Dissertation/Thèse

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2019
Thèses
1
  • JOÃO HENRIQUE NASCIMENTO PATRIOTA
  • Orientation selectivity in cat and agouti primary visual cortex as reflected in firing rates, LFP gamma oscillations and phase relationships 

  • Leader : KERSTIN ERIKA SCHMIDT
  • MEMBRES DE LA BANQUE :
  • EMELIE KATARINA SVAHN LEAO
  • RALF ALBERT WERNER GALUSKE
  • KERSTIN ERIKA SCHMIDT
  • Data: 28 févr. 2019


  • Afficher le Résumé
  • Even though several mammalian orders have orientation-selective neurons, these neurons can be organized in different functional cortical layouts. A prominent example is the columnar orientation preference map found in carnivores (cats, ferrets, tree shrews) and all primates (e.g. human, macaque, mouse lemur) studied so far, as opposed to the seemingly random arrangements commonly referred to as salt-and-pepper configurations, observed in rodents. Orientation selectivity is generally deduced from stimulus-driven spiking activity. However, it has also been observed in oscillations of the local field potential (LFP), especially in the gamma band. In several of the species expressing a columnar map, preference orientation of spiking activity and gamma power are similar. This is compatible with the interpretation that the LFP samples activity from contiguous cortical patches responding to the same orientation. Spikes can be strongly locked to certain phases of LFP oscillations, and the latter are thought to not only establish temporal windows coordinating spiking activity of local neuronal populations but to also enable communication between distant neuronal populations. We thus hypothesized that a columnar/non-columnar functional layout might also be reflected in spike-field interactions.

     

    In the present thesis, we examined spikes and LFP oscillations in the low gamma (low-γ) band of +/-30-50 Hz obtained from multiple parallel recordings in visual cortex during grating stimulation in two representatives of different mammalian order and similar V1 size but different functional layouts – the domestic cat for carnivores, and the Amazonian agouti for rodents. Previously, we observed that although agoutis possess orientation selective neurons they do not express columns as cats do. We correlated the orientation tuning of spikes with that of the low-γ power of the same electrode. This analysis revealed that units exhibiting both orientation selectivity in spikes and LG power (OSI > 0.1) exhibit similar preference in cats (n = 95, circular correlation = 0.56, p = 1.44e-12), but much less in agouti (n = 39, circular correlation = 0.40, p = 0.0067). Further, we evaluated if single unit spiking activity is coordinated with the LFP in the Gamma range recorded from the electrode as reflected in phase-locked events. In cats,  phase-locked events frequently occurred in an orientation- selective manner and with similar orientation preference as the spiking activity (n = 33, circular correlation = 0.57, p = 0.0035). In contrast, agouti showed only very few phase-locked events and those were not correlated with spike orientation selectivity (n = 6, circular correlation coefficient = 0.11, p = 0.79).

     

    Our results support the notion that the coordination of spiking and LFP gamma power in cats could be related to their orderly columnar layout. Along the same line of argumentation, we propose that the lower similarity of spike and gamma tuning and the lack of selective phase-locked events in agouti reflects a lesser or absent organization of orientation preference in a contiguous columnar layout in this species.

Thèses
1
  • GUSTAVO BALBINOT
  • Compensatory relearning following stroke: motor map plasticity and recovery following intensive enriched reaching rehabilitation

  • Leader : MARTIN PABLO CAMMAROTA
  • MEMBRES DE LA BANQUE :
  • MARIA BERNARDETE CORDEIRO DE SOUSA
  • ALINE DE SOUZA PAGNUSSAT
  • CLAUDIO DA CUNHA
  • DIEGO ANDRES LAPLAGNE
  • MARTIN PABLO CAMMAROTA
  • Data: 22 févr. 2019


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  • Over the past decades, Brazilian population over 60 years of age has increased, as well as chronic diseases related to aging. Among these, stroke, one of the main causes of hospitalizations and mortality in Brazil; causing some type of disability to perform activities of daily living to the majority of patients. Understanding how the rehabilitation process occurs, such as the remodeling of motor maps and motor pathways is of utmost importance. The study of this phenomenon can lead to optimization of rehabilitation and to a better understanding of how drugs can act to restore brain function following stroke. In addition, lesion location and severity are determinant for the level of motor impairment following the insult. Preliminary results obtained by PhD Numa Dancause and PhD Dale Corbett research teams indicated that when the lesion encompass the dorsal striatum, motor representations are extremely impaired. Therefore, it was hypothesized that the dorsal striatum has a determining role in the constitution and possible remodeling of the cortical maps during motor relearning. In addition, subcortical structures may increase activity and assume a more active role in the expression of motor behavior. In this thesis we develop a new methodology to quantify and better understand changes of upper limb movement following stroke in rodents (rats: Article 1; mice: Article 2). Next, we review the main pathways and mechanisms involved in motor relearning following stroke (Article 3). Finally, the main article of this thesis demonstrates how intensive rehabilitation promotes cortical motor map plasticity (Article 4). Intensive rehabilitation led to motor map expansion, increased kinematic movement of the paretic limb, and increased use-dependent activity of compensatory brain regions, such as the contralesional cortex and red nucleus. Here, we propose an intertwined mechanism for severe stroke recovery, which involves bilateral and bi-hemispheric interactions. In short, this thesis corroborates that rehabilitation promotes expansion of cortical motor representations; and advances the knowledge about compensatory recovery following severe stroke in rats.

2
  • DANIEL GOMES DE ALMEIDA FILHO
  • Corticalization of hippocampal-dependent memory during REM sleep - Investigating different time windows after learning

  • Leader : SIDARTA TOLLENDAL GOMES RIBEIRO
  • MEMBRES DE LA BANQUE :
  • MÁRCIO FLÁVIO DUTRA MORAES
  • ADRIANO BRETANHA LOPES TORT
  • KOICHI SAMESHIMA
  • SIDARTA TOLLENDAL GOMES RIBEIRO
  • RODRIGO NEVES ROMCY PEREIRA
  • Data: 25 févr. 2019


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  • Sleep and memory are two essential aspects of the life of most living beings. During sleep we rest our muscles and our internal organs, reduce energy expenditure, recover our immune system, and clean our brains from metabolites; everything necessary to prepare our body for the next day of experiences. Simultaneously, memory is a cognitive function that allows us to characterize patterns, store them, build and develop ideas, and define who we are. Interestingly, the last decades of research had led to the notion that these two important physiological processes may keep holding hands, i.e., that the sleep function on memory is not merely by cleaning unnecessary information and passively helping by increasing the signal-to-noise ratio. The new evidence suggest a protagonism of sleep in actively working on memory processing. Besides the plentiful evidence implicating a specific phase of sleep called non-rapid eye movement (NREM) in memory consolidation, the present work focus on understanding the mechanism by which REM sleep benefits hippocampal-dependent memory processing. We have gone into an extensive review of the literature, collaborations, designing, performing, and analyzing experiments aiming at step forward in the understanding the role of REM sleep in the process of making hippocampal-dependent memories persist and gradually depend on neocortical structures (corticalization) over time. Our results indicate that there are special time windows for REM sleep-dependent plasticity and memory corticalization after learning, with particular attention to an early window 3 – 4h after training and a late one about 12h after. We show evidence of an interplay between the hippocampus and the retrosplenial cortex (two regions closely related to memory processing) during REM sleep, and that this interplay in the early window is correlated with memory expression. We also exhibit evidence that the upregulation of genes related to synaptic plasticity during the late time window, which have been consistently implicated in memory persistence, may depend on REM sleep. Altogether, the results reported in the present work support the notion that windows of REM sleep after training are important for offline memory processing and corticalization. They also suggest that the mechanisms of REM sleep action comprise the cross-talk between memory-related cortical and subcortical regions, and to provide training-induced gene expression necessary for the optimized remodeling of cortical networks for the introduction of new information into preexisting knowledge

3
  • MARINA PÁDUA REIS
  • On the role of the perirhinal cortex in object recognition memory reconsolidation

  • Leader : MARTIN PABLO CAMMAROTA
  • MEMBRES DE LA BANQUE :
  • MARTIN PABLO CAMMAROTA
  • FLAVIO FREITAS BARBOSA
  • CYNTHIA LORENA KATCHE
  • ANA CAROLINA LUCHIARI
  • DIEGO ANDRES LAPLAGNE
  • Data: 14 mars 2019


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  • Consolidated memories can become labile when reactivated and, to persist, must undergo a protein synthesis-dependent restabilization process called reconsolidation. The perirhinal cortex (PER) regulates the flow of information between different brain areas and although it has been implicated in object recognition memory (ORM) reconsolidation, the actual role of PER in this process remains controversial. Using the novel object recognition task we investigated the conditions that constrain PER involvement in ORM reconsolidation. We found that bilateral intra-PER infusions of the protein synthesis inhibitor anisomycin caused amnesia when administered immediately after ORM reactivation in the presence of a familiar object but not when memory was reactivated in the presence of a new object, two familiar objects, or a new object alongside a familiar one. Immunofluorescence analyses revealed a prominent increase in PER ZIF268 expression only after ORM reactivation in the presence of a single familiar object. We also found that PER NMDAr blockade with the selective NMDAr antagonist AP5 and ZIF268 expression knockdown with antisense oligonucleotides hindered ORM reconsolidation. Our results indicate that partial perception of recognition cues during memory reactivation is a boundary condition for the participation of PER in ORM reconsolidation, and suggest that this process involves NMDAr activation and ZIF268 expression in that cortex.

2018
Thèses
1
  • RAFAEL HUGO DE ANDRADE PEDROSA
  • IMPLEMENTATION OF PLACE CELL RECORDINGS USING MOVABLE TETRODES IN RATS

  • Leader : ADRIANO BRETANHA LOPES TORT
  • MEMBRES DE LA BANQUE :
  • HINDIAEL AERAF BELCHIOR
  • RODRIGO NEVES ROMCY PEREIRA
  • CLEITON LOPES AGUIAR
  • ADRIANO BRETANHA LOPES TORT
  • Data: 9 avr. 2018


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  • The formation of spatial maps depends on the hippocampus and associated structures. Electrophysiological activity in the CA1 region of the hippocampus encodes spatial representations through increases in the firing rate of pyramidal neurons, known as place cells. The present work aimed the implementation of hippocampal electrophysiological recording technique through the use of microdrives of multiple movable tetrodes. For this, we developed a microdrive prototype and performed stereotaxic surgeries in rats for bilateral chronic implant. The new prototype microdrive contained 16 movable tetrodes and allowed the individual progressive positioning of the tetrodes in the pyramidal layer of CA1 region of the dorsal hippocampus. After the surgical recovery of the animals, we recorded the extracellular electrophysiological activity of the CA1 region while rats searched for water reward at the ends of a linear track. The waveforms of recorded action potentials were then classified as individual neural units by semi-automatic classification algorithms. Each firing of a given neuron was then associated with the instantaneous position of the rat on the linear track, which allowed for detecting place fields of the place cells. We have thus validated the microdrive prototype we developed and, thereby, provided an important methodological basis for future studies aiming to understand the spatial encoding of the environment and the formation of spatial memories.

2
  • GÊNEDY KARIELLY DA SILVA APOLINÁRIO
  • Object recognition memory reconsolidation and PKMζ

  • Leader : MARTIN PABLO CAMMAROTA
  • MEMBRES DE LA BANQUE :
  • DIEGO ANDRES LAPLAGNE
  • FLAVIO FREITAS BARBOSA
  • MARTIN PABLO CAMMAROTA
  • Data: 18 juil. 2018


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  • Remembering facts and events requires object recognition memory (MRO). Reconsolidation integrates new information into MRO through bidirectional changes in hippocampal synaptic efficacy and BDNF signaling. In turn, BDNF enhances long term potentiation (LTP) through protein kinase Mζ (PKMζ), which might preserve memory by controlling AMPAR function. However, the possible involvement of PKMζ in ORM reconsolidation has not yet been studied. In rats, we found that hippocampal PKMζ inhibition with zeta-inhibitory peptide (ZIP) or antisense oligonucleotides, but not PKCι/λ inhibition with ICAP, hindered retention provided MRO was reactivated simultaneously with the introduction of a novel object. Similarly, ORM reactivation increased hippocampal PKMζ only when it happened in the presence of an unfamiliar object. BDNF co-infusion reversed the amnesia induced by post-reactivation hippocampal protein synthesis inhibition but not that triggered by ZIP, which did not affect spontaneous oscillatory activity. Moreover, reduction of hippocampal AMPAR surface expression after MRO reactivation hampered retention, whereas blockade of AMPAR endocytosis increased PSD GluA1/GluA2 and reversed the amnesic effect of ZIP. MRO consolidation, but not reconsolidation, requires protein synthesis in entorhinal cortex (CE). We found that animals rendered amnesic by intra-CA1 ZIP reacquired MRO upon retraining, but inhibition of CE protein synthesis impaired relearning as if MRO had to be consolidated anew. Our results show that hippocampal PKMζ acts downstream BDNF to regulate AMPAR recycling at the time of reconsolidation and indicate that PKMζ inhibition during this process deletes MRO.

     

3
  • RODRIGO MARQUES DE MELO SANTIAGO
  • Memory Reconsolidation and Extinction: A Computational Approach

  • Leader : ADRIANO BRETANHA LOPES TORT
  • MEMBRES DE LA BANQUE :
  • ADRIANO BRETANHA LOPES TORT
  • JANINE INEZ ROSSATO
  • OLAVO BOHRER AMARAL
  • Data: 20 août 2018


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  • he reconsolidation and extinction of aversive memories and their boundary conditions have been extensively studied in order to outline better strategies for the treatment of fear and anxiety related disorders. In 2011, Osan et al. developed a computational model for exploring such phenomena based on attractors dynamics, Hebbian plasticity and synaptic degradation induced by prediction error. This model was able to explain in a single formalism several experimental findings regarding the freezing behavior of rodents submitted to paradigms of contextual fear memory consolidation, reconsolidation and extinction. In 2017, Radiske et al., based on experiments in rats subjected to the inhibitory avoidance task, found that the previous knowledge of the current aversive context as non-aversive is a boundary condition for the reconsolidation of the shock memory experienced in that context. In the present work, we aimed to investigate whether the formalism introduced by Osan et al. (2011) is sufficiently general to explain the behavioral results described by Radiske et al. (2017). To do so, we first implemented the Osan et al.'s (2011) model in an open programming language (Python) and validated it through the replication of the main results reported in the original publication regarding contextual fear conditioning. Then, we adapted the model to simulate experimental protocols in the inhibitory avoidance task employed by Radiske et al. (2017). The results show that the boundary condition found by Radiske et al. (2017) is compatible with the dynamics of an attractor network that supports a synaptic labilization system common to reconsolidation and extinction. Finally, by scanning some model parameters – such as the levels of protein synthesis and degradation –, we provide behavioral predictions in the inhibitory avoidance task that can be tested experimentally.

4
  • CAROLINE PEREIRA DE ARAÚJO
  • BEHAVIORAL  CHANGES  INDUCED  BY  INTRA-HIPPOCAMPAL  ADMINISTRATION  OF PILOCARPINE: RELEVANCE FOR THE STUDY OF COMORBIDITIES IN ANIMAL MODELS OF TEMPORAL LOBE EPILEPSY

  • Leader : CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
  • MEMBRES DE LA BANQUE :
  • BEATRIZ DE OLIVEIRA MONTEIRO
  • CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
  • MARTIN PABLO CAMMAROTA
  • Data: 31 août 2018


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  • Temporal Lobe Epilepsy (TLE) is the most common form of focal epilepsy. The human condition can be modeled in animals by the systemic administration of pilocarpine (PILO) or kainic acid (KA). The experimental approach involves an initial insult (status epilepticus - SE) resulting in wide-spread cell death, structural reorganization, chronic spontaneous seizures and, impaired performance in memory tasks and anhedonia. The identification of the anatomical substrates related to the cognitive impairments in those models is not entirely known, since systemic administration may lead to multiple epileptic foci. To minimize the impact of spatially distributed, numerous epileptic foci, on cognitive performance, we present a protocol in which the convulsant agent is administered directly in the target structure of interest (i.e., straight into the hippocampus). This approach has been used for KA in mice, but no systematic study has evaluated the effects of intrahippocampal administration of PILO. Here, we described the acute and chronic behavioral effects of the intrahippocampal administration of PILO (4 doses: 70, 245, 400 e 700 µg, in 1 µL) in mice during isoflurane anesthesia. KA (20 mM, 50 nL) and saline (0.9 %) were used as positive and negative controls, respectively. The results show a correlation between the severity of the SE and
    the dose of PILO given (measured acutely by behavioral scores and indirectly through the evolution of weight). Interestingly, intrahippocampal PILO injection (N=62) did not elicit tonic seizures, as commonly observed after systemic administration which contributed to the low mortality rate of the model (4 out of 63 and 10 out of 11, respectively). In the chronic phase (1 month after SE), mice treated with high doses of PILO and KA presented spontaneous seizures. Behavioral tests revealed that epileptic animals (independent of the convulsive drug used) present higher stereotyped ambulation (in the open-field) than animals from the control group. In hippocampal-dependent memory tests, PILO treatment, especially at high doses, impaired performance in the object
    recognition task, but not in the Barnes maze. Animals from the KA group presented impaired performance in all memory tests compared with the PILO group (high dose). Taken together, our results demonstrate that ihpc
    administration of PILO in mice results in spontaneous and recurrent seizures, as well as moderate cognitive impairment (compatible with comorbidities observed in humans with TLE), and low mortality rate. We believe that the present model has face validity for human TLE, and may serve as an alternative to KA models (which are expensive) and to the route of administration (high mortality when PILO is administered systemically).

5
  • BRUNA SANTOS DE CARVALHO
  • INFLUENCE OF THE ELECTRICAL ACTIVITY ON SPECIFICATION OF NEURAL PROGENITORS OF THE ADULT SUBVENTRICULAR ZONE

  • Leader : EDUARDO BOUTH SEQUERRA
  • MEMBRES DE LA BANQUE :
  • EDUARDO BOUTH SEQUERRA
  • CECILIA HEDIN PEREIRA
  • EMELIE KATARINA SVAHN LEAO
  • Data: 31 août 2018


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  • The Subventricular zone (SVZ) is the site of adult neurogenesis to the olfactory bulb (OB). SVZ progenitors generate mainly two types of interneurons that integrate in the OB: granular and periglomerular (PG) neurons. These cells can also be further subdivided based on the expression of the proteins calbindin, calretinin or tyrosine hydroxylase. The mechanisms that lead to the specification into these neuronal types are unknown. In the spinal cord neurogenesis, neurotransmitter identity is specified according to early spontaneous electrical activity in progenitor and precursor cells. This electrical pattern guide master transcription factors expression and the differentiation in a particular subtype. Manipulation of electrical activity can change de fate of progenitors and derived neurons.  We hypothesize that the specification of SVZ-OB interneurons could also be influenced by electrical activity.  To test this hypothesis, two experiments were designed to manipulate the cell electricity either acutely or chronicly. First, DCX-Cre-ER2/lox-GFP mice were injected with Kainic Acid (KA) or PBS in the neuroblasts migratory route to the bulb. Tamoxifen was injected 4 days after to label immature neuroblasts affected by KA and perfusion was performed 45 days after KA injection.  In a second set of experiments, wild type mice were injected with a retrovirus containing the RNA for the expression of NaChBac, a bacterial sodium channel that increases electric activity. This channel is fused with the GFP that labels the infected cells. To control this experiment, a mutated non-functional version of the NaChBac channel was used. Cell identity was analyzed 45 days after injection. Our preliminary results suggest that the neuroblasts stimulated by the acute approach differentiate into TH+ PG neurons at the expense of Calbindin+ PG phenotype

6
  • ANA RAQUEL MELO DE FARIAS
  •  REPROGRAMMING OF ASTROGLIAL CELLS INTO NEURONS USING A COCKTAIL OF SMALL MOLECULES

  • Leader : MARCOS ROMUALDO COSTA
  • MEMBRES DE LA BANQUE :
  • CECILIA HEDIN PEREIRA
  • MARCOS ROMUALDO COSTA
  • EMELIE KATARINA SVAHN LEAO
  • Data: 28 nov. 2018


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  • The reprogramming of different specialized cell types in others has been a field widely studied in recent years. More specifically, the generation of induced neurons (iNs) is used with the objective of applying these cells in the study of pathological models and in cellular therapy, focusing on the treatment of patients with neurodegenerative diseases or acute lesions in the central nervous system. Several methodologies have been used for this approach, including the reprogramming of cells from other lineages into neurons, either directly or indirectly. However, most of the cellular reprogramming protocols depend on the overexpression of ectopic genes, which may lead to other transient changes not desired in reprogrammed cells. In order to overcome these possible side effects, we investigated the possibility of reprogramming astrocytes from postnatal mice into neurons through the transient exposure of the cells to a cocktail of small molecules added to the cell culture medium. This cocktail includes molecules that act in different cellular pathways, among which the regulation of gene expression, the modulation of neurogenesis and the control of the cell cycle, previously been used in the reprogramming of fibroblasts into neurons. To demonstrate the phenotype of the cells after treatment with the cocktail, aspects such as the expression of typically neuronal and astrocytic proteins, morphology, survival, proliferation and gene expression were evaluated through the techniques of immunocytochemistry, time-lapse video-microscopy and RT-qPCR. Based on the data obtained it was observed that the drug cocktail used induced in the treated astrocytes an increase in the expression of genes related to the neuronal profile and a significant change in its morphology, although this is not typical of neurons. Thus indicating that the combination of small molecules used is not sufficient to effectively reprogram astrocyte cells into induced neurons.

7
  • LUANA DANTAS DA SILVA
  • GAMMA FREQUENCY DECAY: COMPARING THE ACTIVITY OF RETINA, LATERAL GENICULATE NUCLEUS AND VISUAL CORTEX

  • Leader : SERGIO TULIO NEUENSCHWANDER MACIEL
  • MEMBRES DE LA BANQUE :
  • JEROME PAUL ARMAND LAURENT BARON
  • KERSTIN ERIKA SCHMIDT
  • SERGIO TULIO NEUENSCHWANDER MACIEL
  • Data: 14 déc. 2018


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  • In addition, the presence of gamma oscillations (30 to 90 Hz) has been implicated in cognitive processes such as perceptual attachment (Singer, 1999; Uhlhaas et al., 2009), attention (Fries, 2001; Gregoriou et al. Pesaran et al., 2002; Montgomery and Buzsáki, 2007) and the temporal expectation (Lima et al., 2011). In the visual system, gamma activity patterns appear at different levels of processing. Gamma activity has been identified as an important mechanism for sensory coding and for controlling the flow of information in cortical-cortical systems, as originally suggested by Pascal Fries (Fries, 2005, Fries, 2009), in his hypothesis of "communication through coherence" (CTC) hypothesis). Recently, experimental work on monkeys has suggested that frequency control may be crucial for neural communication, for example between cortical areas V1 and V4 (Bosman et al, 2012). Furthermore, it has been demonstrated that different frequencies can be used as distinct channels for information transmission, such as between FEF and V4, a mechanism also described in the hippocampus (Colgin et al., 2009). In this way, it is possible that the frequency is a fundamental parameter for the control of gamma oscillations. In fact, some studies indicate that frequency may vary according to the attention load (Bosman et al, 2012). The present study makes comparisons between the gamma generated by very different mechanisms: 1) the retinogeniculate system of the anesthetized cat and 2) the primary visual cortex of the capuchins agreed. We observed a strong decay along the responses in these two systems. Three adult monkeys (Capuchinhos sapajus libidinosus and Sapajus nigritus, male and female) and 4 adult cats participated in this study. Our data shows that the decay of gamma frequency in the primary visual cortex (awake monkey) is surprisingly similar to that observed in the retinogeniculate system (anesthetized cat).

Thèses
1
  • PRISCILA TAVARES MACÊDO
  • INVESTIGATION OF INITIAL SYMPTOMS OF ALZHEIMER'S DISEASE IN WISTAR RATS AFTER INTRACEREBRAL INFUSION OF AMYLOID PEPTIDES AND THE NEUROPROTECTIVE POTENTIAL OF ERYTHRINA VELUTINA EXTRACT IN BARNES MAZE

  • Leader : REGINA HELENA DA SILVA
  • MEMBRES DE LA BANQUE :
  • RODRIGO NEVES ROMCY PEREIRA
  • VANESSA COSTHEK ABILIO
  • FLAVIO FREITAS BARBOSA
  • MARIA BERNARDETE CORDEIRO DE SOUSA
  • REGINA HELENA DA SILVA
  • Data: 30 janv. 2018


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  •  

    Alzheimer’s disease (AD) is present in 25 million people in the world, and is characterized by the progressive decline of cognition, mainly episodic memory. AD is multifactorial, and the accumulation of amyloid peptides (Aβ) is the main proposed mechanism underlying neurodegeneration. Aβ are the main components of the amyloid plaques in the brain, that are physiopathological hallmarks of the disease. Intracerebral infusion of Aβ in rats is usually used as an animal model of DA and generates the accumulation of these peptides in the brain together with spatial memory impairment. However, most studies show moderate to severe deficits after chronic Aβ infusion, without evaluation of possible subtle initial deficits. The study of the initial stages of AD is relevant for mechanicistic and therapeutic investigations. The Barnes maze has been used for investigating deficits in the hippocampal function in rats. The animals are exposed to a circular apparatus with holes in its periphery. One of the holes is connected to a safe place. In this task, rats navigate guided by distal cues to find this safe compartment. The performance of the animals in the training phase (repeated exposures to the apparatus with the safe box placed in the same position) and test probe (reexposure after variable intervals without the safe box) is used to the evaluation of acquisition and retrieval of the spatial task, respectively. The evaluation is conduct by parameters of general performance (latency and distance to reach target, number of errors, among others) and by a specific analysis of search strategies. In this way, the animal use spatial information and move directly towards the target (direct strategy), visit sequential holes until reach the target (serial strategy) or visit holes in a non-systematic fashion until reach the target (aleatory search). The analysis of strategies allows the detection of alterations in the mode of solution of the task, even if a given experimental approach does not modify the general performance parameters. In the present study, we aimed to investigate possible initial cognitive signs of AD in Wistar rats submitted to intracerebral infusions of Aβ, as well as the effects of a potentially neuroprotective treatment, by the evaluation of spatial memory in the Barnes maze. We used the alkaloid extract of Erythrina velutina (“mulungu”), which was previously studied for anxiolytic, anti-inflammatory, antioxidant and cholinergic actions. First, we standardized the task to our experimental conditions, and verified a possible influence of repeated expositions to the apparatus (for future long-term protocols) or of the implantation of the cannulas in the brain. Rats went through (or not) to implantation of cannulas (bilaterally in the hippocampal CA1 and in the lateral ventricle) and were exposed to 5 sequences of exposition to the Barnes maze (4 trainning sessions with 4 trials each, a 24h test and a 10-day retest sessions). Results showed that rats learned the task, showing diminished latency and distance to target, decreased erros and increased target quadrant exploration across the trials of all sequences. Both groups showed task retrieval, and there was a slightly improved performance in the implanted group. We concluded that the task can be held repeatedly, and in implanted animals, without altering the performance. In the second phase, we investigated the use of different strategies in the Barnes maze by rats submitted to the presence of absence of distal cues. Rats were exposed to the training phase, and in the probe session (24 h later) half the animals were exposed to the maze in the presence of the same distal cues used in training (spatial group), while the other rats went through the probe test without those cues (a black curtain was placed around the maze – non-spatial group). Both groups learned the task, but the spatial group preferred the used of direct strategies, while the non-spatial group preferred other strategies. We concluded that the removal of distal cues does not hinder the execution of the task, and the animals use alternative search modes under this condition. In the third phase (two experiments) we verified the effects of the intracerebral infusion of Aβ on the acquisition and retrieval of Barnes task. In experiment 1, rats received 15 daily i.c.v. infusions of saline or Aβ (30, 100 ou 300 pmol) plus bilateral CA1 infusions in the first day, and were exposed to 3 sequences of Barnes task (training, 24h test and 10-day retest in each sequence). Sequence I was held before surgery (all the animals learned the task), II started at 11th infusion and III started 10 days after II. The behavior of the Aβ-treated animals varied greatly at sequences II and III, and hence no differences were observed. There was high mortality due to treatment. At the end of the behavioral sessions, saline and Aβ 30pmol groups were euthanized for Aβ immunohistochemistry. The analysis by relative optical density showed increased Aβ staining in the hippocampus and neocortex. We concluded that, although there was Aβ deposition, the treatment did not induce performance deficits. In experiment 2 we investigated the effects of Aβ (30 pmol) infusion on the search strategies in the Barnes maze. Animals went through one sequence of Barnes task (4 trainings with 2 trials each and a 3-day test, in order to increase difficulty). In the probe test, although Aβ animals showed some retrieval, they showed preference for non-spatial strategies, opposed to saline-treated rats. We concluded that Aβ infusion induced subtle alterations in spatial memory, compatible with the initial stages of AD, which is relevant for investigations of potential neuroprotective approaches. In the last stage, animals submitted to the same infusion protocol described above were concomitantly treated orally with 200 mg/kg of mulungu extract and went through 2 Barnes task sequences. In general, no differences were observed among the groups in acquisition or retrieval. Thus, we concluded that the protocol used here was not able to detect a beneficial effect of mulungu extract in the Aβ infusion AD model. 

2
  • KELLY SOARES FARIAS
  • USING ASTROCYTES AS DISEASE-MODIFYING TREATMENT FOR TEMPORAL LOBE EPILEPSY

     

  • Leader : CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
  • MEMBRES DE LA BANQUE :
  • OLAGIDE WAGNER DE CASTRO
  • CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
  • EDUARDO BOUTH SEQUERRA
  • RODRIGO NEVES ROMCY PEREIRA
  • BEATRIZ DE OLIVEIRA MONTEIRO
  • Data: 28 févr. 2018


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  • Astrocytes are specialized glial cells involved in the extracellular homeostasis by buffering potassium cation (K+) concentration, metabolizing neurotransmitters, controlling neuronal firing and synchronization and contributing to the blood-brain barrier. Under pathological conditions, astrocytes may change their morphology in order to compensate abnormal function, being referred to as activated astrocytes (reactive gliosis). This phenomenon is commonly observed in brain regions associated with seizure generation and spread, although its role in abnormal synchronization is unknown. While astrocytes can enhance potassium and glutamate-related metabolism, sustained long-term reactivation can lead to neuronal dysfunction. Temporal lobe epilepsy (TLE) is the most common form of epilepsy and is usually associated to refractoriness. TLE is characterized by extensive cell death (hippocampal sclerosis), synaptic reorganization (mossy fiber sprouting) and reactive gliosis. Here, we hypothesize that transplantation of immature astrocytes in chronically epileptic hippocampus would reduce epileptiform activity, including the occurrence of electrographic and behavioral seizures. To test this hypothesis, animals made epileptic by the systemic injection of pilocarpine (which induced status epilepticus, SE) were unilaterally transplanted with green fluorescent protein-positive (GFP) astrocytes into the hippocampus 30 days after the SE. Group assignment (SE-Saline e SE-Astro GD) was made according to SE behavioral severity and spontaneous epileptiform activities (interictal spikes, high-frequency oscillations, seizures) were recorded in both (treated and untreated) hippocampi using chronically implanted multi-electrodes. Astrocytes had migrated approximately 1500µm injection site, and survival rate was 1%. Astrocytes were found in the host hippocampus seven months after transplantation and were mainly localized at the hilus, at the granular layer of the dentate gyrus, at molecular layer of hippocampus. Cells or tissue clusters indicative of tumor were not identified. In a second group, astrocytes were found in the cortex and constituted the SE-Astro Cortex group. No difference was found in epileptiform activity recorded between groups. Epileptiform electrographic activity was recorded in 80% of control animals (SE-Saline, N= 8/10, in 80% of SE-Astro Cortex group (SE-Astro Córtex, N=4/5) and in 60% of animals that received astrocytes into the hippocampus (SE-Astro GD, N=2/5). Spontaneous seizure occurrence was variable between animals (21 vs 12 vs 1 recorded seizures in SE-Saline and SE-Astro Cortex and SE-Astro GD groups, respectively), however, no difference was observed in seizure frequency between groups (seizures/hour: 0.05±0.01 vs 0.03±0.003 vs 0.02, SE-Saline, SE-Astro Cortex and SE-Astro GD, respectively). Astrocytes grafting did not change seizure duration (67.5 ± 3.6 s vs 74.2 ± 3.9 s vs 65.3 s for SE-Saline, SE-Astro Cortex and SE-Astro GD groups, respectively). Also, we did not observe any difference in the morphology, periodicity or frequency of hippocampal interictal spikes between experimental groups and/or treated hemisphere. Additionally, however, the animals of SE-Astro Cortex group showed reduced behavioral seizure severity (scores: 5 ± 0.1 vs 4 ± 0.4; for SE-Saline and SE-Astro Cortex, respectively; p =0.02, Mann-Whitney test). SE-Astro GD group animals showed only one spontaneous seizure, and therefore not a candidate for statistics. Even thought the small sample size, our results present the cell therapy relevance for the treatment of epilepsies and reinforce importance of transplantation site for epileptiform activity reduction.

3
  • DARDO NAHUEL FERREIRO
  • Functional properties and spatial layout of neurons in the primary visual cortex: electrophysiological comparison between the Amazonian agouti and the domestic cat.

  • Leader : KERSTIN ERIKA SCHMIDT
  • MEMBRES DE LA BANQUE :
  • KERSTIN ERIKA SCHMIDT
  • CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
  • CRISTOVAM WANDERLEY PICANÇO DINIZ
  • EMELIE KATARINA SVAHN LEAO
  • JEROME PAUL ARMAND LAURENT BARON
  • Data: 27 mars 2018


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  • So far, there is no evidence of a columnar orientation preference map in rodent primary visual cortex, such as commonly observed in carnivores and primates. At the same time, orientation selective neurons have been found in all rodent species investigated, though interspersed. This opens up the question whether the connectivity underlying the emergence of selective cortical response properties in animals with interspersed as compared to columnar maps follows a different blueprint. Rodent data are so far mainly available for species with nocturnal or crepuscular habits and small brain size, two factors that could also contribute to develop a different functional architecture.


    Therefore, we set out to compare the functional architecture of the primary visual cortex of carnivores with that of a big rodent with diurnal habits, and a V1 size comparable to cats and small primates. To this end, we performed multi-site electrophysiological recordings using spatial arrays from both anesthetized cats’ (Felis catus) and agoutis’ (Dasyprocta aguti) visual cortex. Visual stimuli consisted of oriented gratings of several spatial and temporal frequencies.


    Agoutis presented much smaller orientation selectivity indices (median OSI = 0.10) than cats (median OSI = 0.19). In order to describe the functional architecture based on the electrophysiological data, we quantified the orientation preference difference between neurons according to the cortical distance between them. As expected, this analysis revealed a characteristic slow decrease in neuronal orientation preference similarity for cats. No such “classical” modularity was found for agoutis, but a clustering of neurons with similar orientation preferences was observed for short ranges (< 250um).


    Overall, our results are consistent with recent literature reporting ‘mini-columns’ of orientation preference in mice, and therefore further prove that the rodents’ interspersed maps are not random, as previously assumed. We cannot confirm, however, recent theoretical literature suggesting that agoutis might have “classical” columnar orientation preference maps. Future research should focus to understand the circuits, which lead to small selective receptive fields in agoutis and great visual performance while adopting a different functional architecture.

4
  • JULIANA ALVES BRANDAO MEDEIROS DE SOUSA
  • Epigenetic inheritance of social behavior and neural circuitry organization of the prefrontal cortex in an animal model of autism
  • Leader : MARCOS ROMUALDO COSTA
  • MEMBRES DE LA BANQUE :
  • MARCOS ROMUALDO COSTA
  • CECILIA HEDIN PEREIRA
  • CLEITON LOPES AGUIAR
  • EDUARDO BOUTH SEQUERRA
  • EMELIE KATARINA SVAHN LEAO
  • RODRIGO NEVES ROMCY PEREIRA
  • Data: 10 août 2018


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  • Autism comprises a heterogeneous group of disorders characterized by sensory, motor, language and mainly social deficits perceived early in childhood. Genetic and epigenetic factors, as well as environmental factors, are strongly involved in the predisposition to autism. Studies in animal models of the disease suggest that these same factors can alter the development of the central nervous system, modifying patterns of differentiation and neuronal maturation and generating a dysfunctional brain circuitry. Therefore, identifying the neural changes in the developing brain can provide clues about the causes and possible treatments of autism. Our group previously characterized the animal model induced by administration of VPA in pregnant rats. We demonstrated that VPA-exposed animals during pregnancy (F1VPA) exhibit "autistic" behaviors in postnatal life, such as hyper locomotion, prolonged stereotypy, and reduced social interaction. Histologically, we detected a reduction in the number of parvalbumin (PV)+ interneurons in the medial prefrontal cortex (mPFC) of these animals compared to controls. Considering the effects of VPA on chromatin structure and DNA methylation, we hypothesized that behavioral and histological changes observed in F1VPA animals would be transmissible for the next generation, independent of new VPA exposures. In this work, we analyzed the behavior and histology of mPFC in F1VPA progeny, hereafter referred to as F2. We observed that these animals present a significant reduction in social interaction and in the frequency of exploratory surveys when compared to control animals. This reduction in social preference, however, was intermediate between that presented by control animals and F1VPAanimals, with the latter showing the most severe deficit in social behavior. On the other hand, we observe neither hyper locomotion, nor alterations in the exploratory ambulation or stereotyped behaviors in F2 animals when compared to the controls. Locomotion, exploration and stereotypies had their profiles normalized with respect to F1VPA animals. In order to test whether behavioral impairments in F2 stemmed from differences in parental care of VPA mothers and control mothers on their offspring, we performed cross-fostering experiments. We observed that F2 animals cared for by control mothers presented low rates of sociability when compared to control animals cared for by control mothers, which corroborates the interpretation that the observed changes in F2 animals are epigenetically inherited. The histological evaluation of cortical tissue revealed an increase in the number of PV+ neurons in the mPFC in F2 animals, suggesting an excitatory/inhibitory imbalance in the fronto-cortical circuitry, also observed in F1VPA animals, but in the opposite direction. Therefore, the data presented indicate that prenatal exposure to VPA induces epigenetic changes in rats that can be transmitted to their offspring. This model may contribute in the future to the identification of genetic signatures associated with the behavioral and histological changes observed in autism.

5
  • BRYAN DA COSTA SOUZA
  • Electrophysiological studies in the hippocampus – developing new methods and investigating the neural code

  • Leader : ADRIANO BRETANHA LOPES TORT
  • MEMBRES DE LA BANQUE :
  • MARCELO BUSSOTTI REYES
  • SIDARTA TOLLENDAL GOMES RIBEIRO
  • NIVALDO ANTONIO PORTELA DE VASCONCELOS
  • CESAR RENNO COSTA
  • ADRIANO BRETANHA LOPES TORT
  • Data: 7 déc. 2018


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  • Extracellular electrophysiology is among the main tools used for studying neural activity. In addition to having a high temporal resolution, this technique is stable enough to allow for recording freely-moving animals. In the last decades, the electrophysiology of the hippocampal formation has received particular attention due to the discovery of its relationship with memory and spatial navigation. Specifically, many spatial correlates have been investigated to understand the basis of neural encoding, such as place cells, which increase their firing rate when the animal is at particular locations of the environment. In this thesis, we present three studies exploring hippocampal electrophysiology through different levels of analysis, which aim at better understanding the different coding mechanisms used by the brain. In the first work, we focus on the problem of spike sorting, which consists in the classification of the waveforms detected by the extracellular recording. We investigated the use of Gaussian mixture models to perform feature extraction and clusterization of the waveforms. After using real and simulated data to evaluate the best strategies of our algorithm, we compared our spike sorting to two other known methods. Our algorithm, which combines two main feature extraction techniques with a new method of dimensionality reduction, showed better, or similar, results compared to the two other spike sorters. In the second work, we analyzed the current metrics used to find neurons presenting some spatial correlate, or information, such as place cells, head-direction cells, and speed cells. Using real and simulated data, we evaluated how the spatial information estimated by each metric correlated to the empirical information obtained using a Naive-Bayes classifier. Our results showed that the two main current metrics fail to detect the information content of neurons with high basal firing rate, and thus bias the universe of spatial correlates to low-firing cells. Finally, in the third work, we explored the differences in the proposed mechanisms underlying place cell firing: rate coding and temporal coding. We analyzed the dynamics of coupling between place cells and theta oscillations, comparing it to the firing rate dynamics. Our results revealed an asymmetry between the two mechanisms, with the theta coupling place cells preceding its major changes in firing rate, which corroborate the hypothesis that temporal and rate coding are independent mechanisms. Beyond that, we found that temporal coding represents more extensively the future positions of the animal than the past ones, suggesting its involvement in trajectory planning. In summary, the results of this thesis contribute to both the understanding of neuronal encoding and the development of new techniques in the field of hippocampal electrophysiology

6
  • ANDRE LUIZ VIEIRA LOCKMANN
  • Neural oscillations coupling olfactory and hippocampal networks

  • Leader : ADRIANO BRETANHA LOPES TORT
  • MEMBRES DE LA BANQUE :
  • DIEGO ANDRES LAPLAGNE
  • RODRIGO NEVES ROMCY PEREIRA
  • MÁRCIO FLÁVIO DUTRA MORAES
  • PABLO DANIEL TORTEROLO MINETTI
  • ADRIANO BRETANHA LOPES TORT
  • EMELIE KATARINA SVAHN LEAO
  • Data: 13 déc. 2018


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  • Local field potentials (LFPs) in the rodent brain exhibit prominent oscillations, which have been suggested to oordinate information flow across neuronal circuits. This thesis investigated oscillations that simultaneously emerge in the rat olfactory and hippocampal systems and supposedly mediate their communication. The main results and insights are presented in four publications – two commentary (1 and 4) and two experimental (2 and 3) papers. Paper 1 discusses the controversial origin of low-frequency LFP oscillations (~ 1 Hz) that appear in the rodent hippocampus during sleep and anesthesia. Do these oscillations reflect internal processing with the neocortex or do they couple to external inputs from rhythmic nasal respiration? This question is experimentally addressed in paper 2. By simultaneously recording nasal respiration and LFPs from urethane-anesthetized rats, we show that the hippocampus exhibits two independent low-frequency oscillations: one that entrains to neocortical “up-and-down” state transitions and another that entrains to the olfactory bulb respiration-coupled rhythm (RR) – and to respiration itself. Paper 3 further shows that the olfactory bulb also drives beta oscillations (10-20 Hz) in the hippocampus. Together, papers 2 and 3 indicate that related network mechanisms generate hippocampal beta and RR: both rhythms are relayed to the hippocampus by entorhinal cortex inputs to the dentate gyrus and, additionally, the phase of RR modulates beta amplitude. Based on our own results and on publications from other groups, in paper 4 we defend that the recently described delta-band oscillations coupling prefrontal cortex and hippocampus correspond to RR. In all, this thesis supports that respiration-coupled and beta oscillations mediate olfacto-hippocampal communication.

7
  • GEISSY LAINNY DE LIMA ARAÚJO
  • Psychophysiological effects of a brief mindfulness-based intervention in healthy young adults

  • Leader : MARIA BERNARDETE CORDEIRO DE SOUSA
  • MEMBRES DE LA BANQUE :
  • TIAGO ARRUDA SANCHEZ
  • MARIA BERNARDETE CORDEIRO DE SOUSA
  • MARIO ANDRE LEOCADIO MIGUEL
  • BRUNO LOBAO SOARES
  • IVANI BRYS
  • Data: 18 déc. 2018


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  • Mindfulness-based training have been used to facilitate more adaptative mechanisms aimed to reduce anxiety, depression, stress, and improve attention regulation, emotions and enhance quality of life. The present study integrates variables related to sustained attention, interoception, affect and stress response in young adults submitted to a three-day training using a mindfulness-based training. The aim of this study is to understand the mechanism by which the mindfulness meditation practice acts acutely regarding to the variables approached.  Electrophysiological, hormonal and behavioral data were collected in two moments, pre and post intervention, in an active control group (n= 20) and an experimental group (n= 20) Our results suggest a difference between groups related to interoception, mindfulness and sustained attention after training. These results are represented through psychological measures and analysis of event-related potentials in one well validated attention task. In addition, intragroup analyzes suggest reduction of anxiety, increased interoceptive sensitivity and state of mindfulness after intervention in the experimental group. Moreover, the data shows lower negative affect and perceived stress in both groups after intervention. In this sense, it is suggested that the brief mindfulness-based intervention impacts on the cognitive performance regarding to an attentional test, with decrease of latency and increase of amplitude of the P300 component. Besides that, increased state of mindfulness, interoception and decrease in the levels of negative affect and perceived stress are also important results consistent with previous findings related to more traditional interventions using mindfulness meditation in a variety of populations

2017
Thèses
1
  • LUÃ CARLOS DE SOUZA
  • THE PROCESSING OF SPATIAL FREQUENCY ACROSS THE CORPUS CALLOSUM DURING MONOCULAR AND BINOCULAR STIMULATION

  • Leader : KERSTIN ERIKA SCHMIDT
  • MEMBRES DE LA BANQUE :
  • EMELIE KATARINA SVAHN LEAO
  • JEROME PAUL ARMAND LAURENT BARON
  • KERSTIN ERIKA SCHMIDT
  • SERGIO TULIO NEUENSCHWANDER MACIEL
  • Data: 28 avr. 2017


  • Afficher le Résumé
  • Neurons in cat primary visual cortex (area 17 and 18) respond selectively to certain stimulus parameters. Such parameters are, for example, contrast, contours of the same orientation and direction of movement, but also the spatial frequency (SF). Differences in SF preference in areas 17 e 18 are thought to emerge from a different distribution of X and Y afferents. The transition zone (TZ), between the two areas has preferences for intermediate SFs. Apart from retino-geniculo-cortical afferents this region also receives dense visual connections through the corpus callosum. It is known that interhemispheric connections are more frequent between visual neurons with a preference for similar orientation and direction. However, data referring to SF selectivity of these connections are still scarce. The objective of the present study is to investigate the functional contribution of interhemispheric visual connections to responses evoked by different SFs in the TZ. While stimulating either monocularly or binocularly with gratings, we investigated the mean rate of neuronal firing in the TZ of anesthetized cats. We observed that, in general, during reversible thermal deactivation of the contralateral visual cortex mean firing rates decreased, but in particular during monocular stimulation of the ipsilateral eye. Moreover, in this condition, responses to the low spatial frequency of 0.15 cycles/degree and to neurons that prefer horizontal contours were more affected. In contrast, with contralateral stimulation, responses to the highest SF of 0.6 cycles/degree and to neurons that prefer vertical contours predominantly decreased their rates. These results indicate that interhemsipheric connections act SF selective. They also suggest that fibers conducting signals driven by the ipsilateral eye through the corpus callosum originate mainly from neurons dominated by Y cells. On the other hand, fibers mediating information from the contralateral eye seem to originate from neurons receiving input from X cells or a mixture of X and Y cells via the retino-geniculate-cortical pathway. The different circuits for low and high spatial frequencies may be involved in a process of binocular interaction, where responses of the ipsilateral eye and the contralateral eye complement each other.

     

2
  • JÉSSICA DE ANDRADE PESSOA
  • ELECTROENCEPHALOGRAPHIC SPECTRAL MARKERS OBSERVED DURING THE ACUTE EFFECTS OF AYAHUASCA AND ITS RELATION TO THE PSYCHEDELIC EXPERIENCE 


  • Leader : DRAULIO BARROS DE ARAUJO
  • MEMBRES DE LA BANQUE :
  • MARIO ANDRE LEOCADIO MIGUEL
  • LUIS FERNANDO FARAH DE TOFOLI
  • DRAULIO BARROS DE ARAUJO
  • Data: 27 juil. 2017


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  • The ayahuasca is a drink with psychedelic properties largely used by indigenous populations from the Amazon basin. It contains the psychedelic tryptamine N,N-dimethyltriptamine (DMT), and monoamine oxidase inhibitors (iMAO), such as harmine and harmaline. The ayahuasca is considered to be a serotonergic psychedelic, capable of inducing an altered state of consciousness with similarities to an oneiric experience, with intense alterations in perception, though, humor, emotion, and mystical-type experiences. The neural correlates of its acute effects have been investigated by different neuroimaging techniques, including electroencephalography (EEG). In this study, we explored EEG spectral changes in 50 healthy volunteers, using a randomized double-blind placebo-controlled experimental design. Half of the volunteers received ayahuasca, while the other half received placebo. After dosing, the volunteers were monitored by an EEG equipment for approximately 4-hours. Aiming to improve data quality, the volunteers were asked to perform 2 simple tasks in three specific moments: before intake, 2h and 4h after intake. For the first task, they should try to stay awake, and alternate moments of eyes open (20 seconds) and eyes closed (40 seconds) for 5 minutes. For the second task, they should keep their eyes closed, trying to stay awake, for another 5 minutes. The spectral analysis (2h) found the alpha power to be significantly lower for the ayahuasca group when compared to placebo in occipital and right temporoparietal regions. Moreover, we found a significant increase in theta power on the right temporoparietal region, also 2h after the intake. Correlation analysis revealed correspondences between the alpha power (2h) and individual scores on two scales used to measure psychedelic effects – the Hallucinogen Rating Scale (HRS) and the Mystical Experience Questionnaire (MEQ). Additionally, we also present curious events found during visual inspection of EEG tracings. Overall, our results suggest that the inhibition of alpha oscillations in posterior brain regions play an important role on the psychedelic experience, maybe sharing mechanisms present during the oneiric experience. 

3
  • BARBARA CIRALLI BOERNER
  • ROLE OF RAT ULTRASONIC VOCALIZATIONS IN SOCIAL LOCOMOTIVE BEHAVIOUR

  • Leader : DIEGO ANDRES LAPLAGNE
  • MEMBRES DE LA BANQUE :
  • DIEGO ANDRES LAPLAGNE
  • FLAVIO FREITAS BARBOSA
  • RODRIGO NEVES ROMCY PEREIRA
  • Data: 18 août 2017


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  • RAT ULTRASONIC VOCALIZATIONS OF FUNDAMENTAL FREQUENCY IN THE 30-90KHZ RANGE KNOWN AS '50 KHZ' USVS, ARE RELATED TO APPETITIVE CONTEXTS SUCH AS SOCIAL INTERACTIONS, REWARD AND MATING. HOWEVER, HOW THESE VOCALIZATIONS CONTRIBUTE TO RAT SOCIAL BEHAVIOUR IS NOT COMPLETELY UNDERSTOOD. PREVIOUS DATA FROM OUR LAB SHOWS THAT THESE USVS ARE TIGHTLY SYNCHRONIZED WITH THE LOCOMOTION OF THE EMITTING RAT, THUS RAISING THE POSSIBILITY THAT VOCALIZATIONS COULD HELP RATS TRACK EACH OTHER IN THE DARK. WE HERE TESTED THIS HYPOTHESIS BY ASSESSING HOW DEVOCALIZING ONE OR BOTH RATS IN A MALE-FEMALE PAIR AFFECTED THEIR SPATIAL INTERACTIONS DURING MATING BEHAVIOR. METRICS OF SPATIAL CORRELATION, SUCH AS AVERAGE DISTANCE BETWEEN THE TWO ANIMALS AND NUMBER AND DURATION OF CHASES WERE ANALYZED FOR EACH RECORD. PRELIMINARY RESULTS SUGGEST THAT, ALTHOUGH DEVOCALIZATION DOES NOT INFLUENCE SUCCESS OF MATING, IT MAY SPECIFICALLY INTERFERE WITH FAST SPATIAL INTERACTIONS.

4
  • RENZO ALVES DANTAS TORRECUSO
  • PROCESSING OF SYNTAX IN MUSIC: AN EEG STUDY

  • Leader : DIEGO ANDRES LAPLAGNE
  • MEMBRES DE LA BANQUE :
  • PETER MAURICE ERNA CLAESSENS
  • EMELIE KATARINA SVAHN LEAO
  • DIEGO ANDRES LAPLAGNE
  • Data: 28 août 2017


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  • In order to make sense out of a sequence of sounds in music, our brain must meaningfully fit and recombine acoustic events into a hierarchic online stream. Although these information units are auditively  delivered in sequences with local connections (one after the other), it is assumed that long term dependencies are established counting on memory traces to sustain recursiveness  in time. Despite theoretical and empirical consensus, there is yet no clear physiological evidence of the temporal dimension of syntactic relations in music.

    We investigated whether there is quantifiable neural activity suggesting the existence of a mental representation for fundamental music syntax rules like tonic-dominant-tonic chords. For such, we compared brain electric activity in 24 subjects (12 musicians, 12 non-musicians) aroused by original and harmonically modified versions of J.S. Bach chorales, using electroencephalography (EEG). Chorales were built by two phrases: initiated by a tonic and arriving in a dominant chord two bars away (first phrase), and concluded in a tonic chord three bars after the dominant (second phrase). Modified versions were created either by elevating or lowering the first, therefore keeping the second phrase intact. We compared the brain electric response for the last chord in both versions.  

5
  • CAROLINA ARAUJO SOUSA
  • POSTNATAL BRAIN MYELINATION IN A MODEL OF AUTISM INDUCED BY PRENATAL EXPOSURE TO VALPROIC ACID

     

  • Leader : RODRIGO NEVES ROMCY PEREIRA
  • MEMBRES DE LA BANQUE :
  • RODRIGO NEVES ROMCY PEREIRA
  • OLAGIDE WAGNER DE CASTRO
  • TARCISO ANDRE FERREIRA VELHO
  • Data: 31 août 2017


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  • The formation of brain circuits during neural development occurs through the interaction between timely regulated genetic and environmental signals, which influence multiple events such as neurogenesis, synaptogenesis, and myelination. In developmental disorders, such as autism spectrum disorders (ASD), deficits in these processes may lead to neural circuitry malformations and, in consequence, to social interaction deficits, restricted interests, and stereotyped movements, among others. Recently, we performed a transcriptome analysis of the frontal cortex of an animal model of autism induced by valproic acid (VPA) in utero in our lab. We observed that VPA animals at the postnatal age 15 (P15) show an increased expression of genes related to synaptic stability and a decrease in the expression of myelin-related genes, suggesting possible molecular mechanisms for the behavioral deficits previously observed in these animals. Therefore, the aim of this Master’s thesis was to further investigate the myelination pattern in the forebrain of VPA-treated rats at different postnatal ages (infant: P15 and adult: P60). For that, experimental and control groups were generated by injecting pregnant dams with 500 mg/Kg i.p. VPA or saline, respectively, on embryonic day 12.5 (E12.5). Analysis of myelin integrity was conducted by two different approaches: (1) gene expression analysis of myelin-related genes (Mobp, Plp1, Mag, and Klhl1) in dissected samples of the frontal cortex of P15 rats by quantitative real-time PCR; and (2) histological quantification of myelin distribution in five sub-regions of the frontal cortex and corpus callosum of P15 and P60 animals. Of all genes analyzed, we observed a significant decrease in Mobp and Mag expression in P15 VPA animals. Myelin analysis showed a significant reduction in myelin staining in the anterior cingulate cortex of VPA animals at P60, but no differences were observed at P15. In conclusion, infant VPA rats showed reduced expression of genes related to myelin assembly, without alterations in the lipid content of myelin in the areas analyzed. Adult animals, in contrast, showed a decrease in lipid content of myelin in the anterior cingulate cortex. Together, these results suggest that communication abnormalities in frontal circuits in this animal model of autism may occur initially due to alterations in myelin organization, leading to myelin reduction in adulthood.

6
  • KÁTIA SIMONE DE ARAÚJO NÓBREGA ROCHA
  • GRATINGS STIMULI DO BIAS OUR CONCEPTS ON CORTICAL GAMMA SYNCHRONIZATION: A STUDY IN CAPUCHIN MONKEY V1

  • Leader : SERGIO TULIO NEUENSCHWANDER MACIEL
  • MEMBRES DE LA BANQUE :
  • JEROME PAUL ARMAND LAURENT BARON
  • KERSTIN ERIKA SCHMIDT
  • SERGIO TULIO NEUENSCHWANDER MACIEL
  • Data: 31 août 2017


  • Afficher le Résumé
  • Cortical gamma oscillations (30 - 90 Hz) have been implicated in various cognitive processes, such as visual binding and attention. So far, most evidence in support of this hypothesis are based on studies that used artificial and simplified stimuli, such as moving gratings and bars. Recently, experimental work using natural images led to conflicting conclusions. In a paradigm that required human subjects to maintain fixation, electrocorticogram signals (ECoG) showed gamma for grating stimuli but not for static images or pink noise (Hermes et al., 2015). On the contrary, analysis of ECoG in the early visual cortex of macaque monkeys revealed strong gamma components for free viewing of natural scenes (Brunet et al., 2015). Here, we aim to clarify these discrepancies using a paradigm that allowed direct comparisons between fixation vs. free viewing conditions, for both simplified stimuli (moving and static gratings) and natural scenes (static and moving images). Recordings of spiking activity and local field potentials (LFPs) were obtained from the central and the peripheral representations of V1. Our results show that in capuchins (N= 3 monkeys), as previously described in macaques and in humans, gamma is characteristically strong when stimulus parameters, such as size, orientation and speed are set at to optimal values. Comparisons between fixation vs. free viewing conditions and gratings vs. natural stimuli revealed that gamma is always strong for optimal grating stimuli, regardless of viewing condition (N= 93 recording sites, 2 monkeys). However, gamma is surprisingly absent during free viewing of natural images and movies. Similar negative findings were also obtained when the monkeys were exposed to real-world scenes, such as objects and other animals in the laboratory. The present results suggest that strong, narrow-band, gamma responses in V1 is primarily associated with the selective activation of cell populations sharing similar response properties. Therefore, gamma may be seen as a resonance phenomenon of the underlying cortical connectivity. Overall, our results belittle the importance of gamma as a key cortical mechanism for vision.

7
  • SUZYANNE XAVIER MACIEL
  • Spontaneous oscillatory patterns in somatosensory cortex in autism model

  • Leader : RODRIGO NEVES ROMCY PEREIRA
  • MEMBRES DE LA BANQUE :
  • EDUARDO BOUTH SEQUERRA
  • RODRIGO NEVES ROMCY PEREIRA
  • CLEITON LOPES AGUIAR
  • Data: 31 août 2017


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  • The rhythmic synchronization of neuronal excitability in neural populations is a crucial mechanism to integrate information between neural networks. In autism spectrum disorders (ASD), it is believed that there is a deficit in the ability to efficiently couple functional neural networks using this mechanism, collectively known as oscillations. In addition, sensory disturbances are one of the most prevalent symptoms in autism, which can be characterized as hyper-responsiveness or hypo-responsiveness, extending to multiple sensory systems, as well as sensorimotor integration. In the animal model of autism induced by prenatal exposure to valproic acid (VPA), it is observed behavioral and cellular alterations similar to those observed in patients with autism. However, there are still few studies evaluating cortical electrophysiological patterns with an emphasis on these oscillations. Therefore, the aim of this study was to evaluate the spontaneous oscillatory activity in local field potentials (LFP) recorded from the somatosensory cortex of rats exposed to VPA and controls. Experimental (n=04) and control (n=04) groups were generated by administration of VPA (500 mg / kg, i.p.) or saline in pregnant rats at E12.5 respectively. When adults, these were anesthetized with urethane and LFP recordings were obtained in the somatosensory cortex using arrays of microelectrodes. Data analysis evaluated the density of spectral power, the occurrence of discrepant events in neuronal activity and the global oscillatory dynamics. Our findings showed that VPA rats have a higher variability of electrophysiological states when evaluated by state-maps derived from spectral characteristics of LFPs in distinct behavioral states. Such variability is mainly influenced by frequencies above 20 Hz (20-55Hz). However, we did not find significant changes in the global analysis of power spectrum bands delta (0.5-4Hz), theta (4-12Hz), beta (12-30Hz) and gamma (30-100Hz). Finally, all VPA animals showed some form of epileptiform activity in the somatosensory cortex in contrast to controls.


Thèses
1
  • RAPHAEL BENDER CHAGAS LEITE
  • Behavioral and Electrophysiological Aspects of Pitch Perception -  A Study of “Absolute Pitch”

  • Leader : CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
  • MEMBRES DE LA BANQUE :
  • PATRÍCIA MARIA VANZELLA
  • EMELIE KATARINA SVAHN LEAO
  • ELIENE SILVA ARAUJO
  • CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
  • WILFREDO BLANCO FIGUEROLA
  • Data: 23 févr. 2017


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  • In humans, the processing of sound information allowed the appearance of language and music. The pitch - which allows the melody of a song and prosody in spoken discourse - is one of these attributes. Pitch perception is a universal skill, however, just a few individuals are able to identify or produce a tone at a particular pitch without an external tonal reference, an ability known as the Absolute Pitch (AP). However, the neural mechanisms responsible for such ability are not yet fully understood. The present work has the objective to contribute to the understanding of the neural processes involved in the perception of pitch in AP possessors. In the first study, we evaluated AP prevalence in a local population of musicians (School of Music, UFRN). For this, we used psychophysical tools and a questionnaire. This first work showed that AP is not an "all-or-nothing" process, but rather that it has different levels of performance: from people that perform below chance, until it increases gradually to 100% of correct answers. While traditional thresholds (~85%) showed a prevalence of AP similar to that observed in musicians in Europe and the United States, the application of a statistical threshold resulted in prevalence similar to that described in populations of music conservatories. In addition, we showed that AP possessors hit more the natural notes (those with the white-keys of the piano) than those that are accidental (flat or sharp, i.e. the black keys of the piano). We also observed that AP possessors present an earlier onset of musical training. Finally, we showed that AP was more prevalent in a high proficiency group in comparison to the average proficiency group. In a second study, we used the auditory brainstem evoked potentials (ABR) to quantify the activation of brainstem nuclei in the processing of heights of individuals with OA. In this work, we showed that sustained responses (but not the transient ones) present a higher energy in individuals with AP than in control musicians. We also found that the amplitude of this sustained response correlates with the reaction time in a pitch naming test. These results suggest that individuals with AP have an increased refinement in the processing of acoustic information in the early stages of auditory processing, which would thus contribute to a greater automation of pitch identification. We believe that this thesis will contribute to the understanding of the relationship between nervous system development and musical learning, thus contributing to the development of new music teaching techniques and training programs.

2
  • BRUNA SOARES LANDEIRA
  • ELIMINATION OF EARLY BORN NEURONS AFFECTS THE SPECIFICATION OF LATE BORN NEURONS IN THE DEVELOPING CEREBRAL CORTEX

  • Leader : MARCOS ROMUALDO COSTA
  • MEMBRES DE LA BANQUE :
  • MARCOS ROMUALDO COSTA
  • MARIANA SOUZA DA SILVEIRA
  • RODRIGO NEVES ROMCY PEREIRA
  • CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
  • JOÃO RICARDO LACERDA DE MENEZES
  • Data: 11 avr. 2017


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  • The cerebral cortex of mammals is histologically organized into in different layers of excitatory neurons that have distinct patterns of connections with cortical or subcortical targets. During development, these cortical layers are sequentially established through an intricate combination of neuronal specification and migration in a radial pattern known as "inside-out":  deep-layer neurons are generated prior to upper-layer neurons.  In the last few decades, several genes encoding transcription factors involved in the specification of neurons destined to different cortical layers have been identified. However, the influence of early-generated neurons in to the specification of subsequent neuronal cohorts remains unclear. To investigate the possible effects early born neurons ablation on the specification of late born neurons, we induced the selective death of cortical neurons from layers V and VI neurons before the generation of neurons destined to layers II, III and IV. Our data shows that one-day after ablation, progenitors resumed generation of layer VI neurons expressing the transcription factor TBR1, whereas virtually no TBR1-expressing neuron was generated at the same developmental stage in age-matched controls. Interestingly, many TBR1-positive neurons generated after deep-layer ablation settled within superficial cortical layers, as expected for upper-layer neurons generated at that stage, suggesting that migration post-mitotic neurons is independent of fate-specification. Furthermore, we observed an increase in  layer V neurons  expressing  CTIP2  and cortico-cortical neurons expressing SATB2 at the expense of layer IV neurons in P0 animals. When these animals became young adults (P30) the increase os SATB2 and CTIP2 neurons is no longer observed, however these neurons are distributed in a different way in somatosensory areas from ablated animals. In vitro experiments show that the laminar cytoarchitectural organization of the cortex is necessary to regenerate the previously deleted TBR1 + neurons. In addition, in vitro experiments indicate that in a condition of low cell density the neurons phnotype is altered, they express several transcription factors at the same time. Together, our data indicate the existence of feedback mechanism either from early-generated neurons to progenitors involved in the generation of upper-layer neurons or from deep-layer neurons to postmitotic neurons generated subsequently. This mechanism could help to control the number of neurons in different layers and contribute to the establishment of different cortical areas.

3
  • NATALIA BEZERRA MOTA
  • MIND MAPPING THROUGH COMPUTATIONAL SPEECH ANALYSIS

  • MEMBRES DE LA BANQUE :
  • RICARDO ALEXSANDRO DE MEDEIROS VALENTIM
  • MAURO COPELLI
  • CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
  • CLAUDIA DOMINGUES VARGAS
  • SILVIA ALICE BURGE
  • Data: 11 juil. 2017


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  • The understanding of complex human behaviors such as language and its variations in different conditions and contexts has been an important research aim for many decades. Naturalistic and quantitative approaches to precisely measure language variations from the structural and semantic points of view have recently emerged, allowing the measurement of variations manifested in free speech that reflect atypical cognitive decline in pathological situations such as psychoses, or typical cognitive development in healthy children during alphabetization, and even the processing of memories in different states of consciousness, such as waking and dreaming. In this work we will start discussing 1) the construction of tools for the analysis of speech structure inspired by the psychopathological descriptions of mental illnesses, 2) their application to the differential diagnosis of psychosis and
    dementias, and 3) the application of semantic tools to predict psychotic episodes. We will proceed by widening this view away from pathology, so as to determine 4) how graph-theoretical measures of language structure vary across healthy cognitive development, and 5) how they relate to indices of academic achievement. Next we will investigate 6) how speech structure varies within a large sample of healthy and psychotic subjects with large age and educational variation (N=200, ages 2-58, kindergarten to PhD), to 7) evaluate the impact of years of education and 8) compare with the development of literature across 5,000 years (N=448 texts; Syro-Mesopotamian (N=62), Egyptian (N=49), Hinduist (N=37), Persian (N=19), Judeo-Christian (N=76), Greek-Roman (N=134), Medieval (n=20), Modern (n=20) and Contemporary (n=31)). We will conclude by applying tools of semantic similarity as a strategy to 9) measure memory reverberation during dreams and their electrophysiological correlates in a sleep
    transition experiment. The results indicate that the structural and semantic tools used in this work can greatly improve the precision of naturalistic measurements of the complex human behaviors expressed in speech.

4
  • MORGANA MENEZES NOVAES
  • IMPACT OF BREATHING TRAINING (PRANAYAMA) ON MARKERS OF ANXIETY, AFFECT, SPEECH, AND FUNCTIONAL MAGNETIC RESONANCE IMAGING (FMRI)

  • Leader : DRAULIO BARROS DE ARAUJO
  • MEMBRES DE LA BANQUE :
  • DRAULIO BARROS DE ARAUJO
  • MARIA BERNARDETE CORDEIRO DE SOUSA
  • ELISA HARUMI KOZASA
  • TIAGO ARRUDA SANCHEZ
  • BRUNO LOBAO SOARES
  • Data: 25 juil. 2017


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  • The systematization of Yoga presented in the Yoga Sutras of Patañjali, written around 400 CE, proposes an eight limb yoga system, also known as Ashtanga Yoga (ashta=eight, anga=limb), consisting of eight set of practices. Among them, the breathing practices, known as Pranayama, has been associated with positive effects on stress and anxiety. This thesis explores the impact of Bhastrika Pranayama training on markers of anxiety, affect, speech, and functional magnetic resonance imaging (fMRI). Thirty young healthy adults, naïve to Yoga practices, were recruited and evaluated by the State-Trait Anxiety Inventory (STAI), the Positive and Negative Affect Schedule (PANAS), Speech Analysis and fMRI (emotional regulation task, and resting state-fMRI), before and after 4 weeks of training Bhastrika Pranayama or control activities. This study is designed as a randomized controlled trial of two parallel arms. The results suggest decreased in both anxiety and negative affect, increased activity in the bilateral anterior insula, right anterior cingulate cortex, right amygdala, and left ventromedial prefrontal cortex (vmPFC). Increased positive affect was correlated with increased activity in right anterior insula and left vmPFC. We also found a positive correlation between increased activity in the left vmPFC and decreased anxiety and negative affect. rs-fMRI results suggest significant decreased functional connectivity in the right anterior insula and right ventrolateral prefrontal cortex (vlPFC) with multiple brain regions known to be involved in emotional processes. Overall, decreased connectivity involving these regions were correlated with decreased anxiety and negative affect, and increased positive affect. Changes in speech analysis were restricted to semantic properties when the words “anxiety”, “negative” and “positive” were used as seeds. These changes correlated with changes in anxiety and affect. In general, our results suggest that the practice of Bhastrika Pranayama leads to changes in anxiety and affect, which was accompanied by changes in the activity and connectivity of brain structures that participate in processes of emotional regulation.


5
  • FERNANDA PALHANO XAVIER DE FONTES
  • The antidepressant effects of ayahuasca, its neural bases and relation with the psychedelic experience.

  • Leader : DRAULIO BARROS DE ARAUJO
  • MEMBRES DE LA BANQUE :
  • ADRIANO BRETANHA LOPES TORT
  • EDUARDO BOUTH SEQUERRA
  • ANDERSON MARCELO WINKLER
  • JOSE NEANDER SILVA ABREU
  • DRAULIO BARROS DE ARAUJO
  • Data: 28 juil. 2017


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  • Recent open label trials show that psychedelics hold promise as fast-onset antidepressants in treatment resistant depression. In Brazil, a psychedelic substance worth mentioning is the ayahuasca. This brew composed by the psychedelic N,N-dimethyltryptamine (DMT), a serotonin and sigma-1 receptors agonist, and reversible monoamine oxidase A inhibitors, such as harmine, harmaline, and tetrahydroharmine, causes changes in perception, emotion and cognition. Preliminary results from our group suggest its antidepressant potential, in addition to demonstrating its safety and tolerability. Although promising, none of these studies have controlled for the placebo effect, which is high in clinical trials for depression. To address this issue, we conducted a parallel-arm, double-blind randomized placebo-controlled trial in 35 patients with treatment-resistant depression. A healthy control group of 50 volunteers was also examined. Patients received a single dose of either ayahuasca or placebo. One day before dosing, and one day after dosing patients were enrolled in a series of tests and assessments, including psychometric scales and fMRI, conducted in the course of a four-day experimental session, to assess changes in different markers of depression. Two clinical scales for depression assessed changes in depression severity: the Montgomery–Åsberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating scale (HAM-D). Assessments were made at baseline, and at 1, 2 and 7 days after dosing. We observed significant antidepressant effects of ayahuasca when compared to placebo at all endpoints. MADRS scores were significantly lower in the ayahuasca group, compared to placebo. Likewise, HAM-D scores were significantly different at D7. Between-group effect sizes increased from D1 to D7. Response rates were high for both groups at D1 and D2, and were significantly higher in the ayahuasca group at D7. Remission rate was marginally significant at D7. In addition, we examined the relationship between the antidepressant and acute psychedelic effects of ayahuasca. The psychedelic effects were assessed using the Hallucinogen Rating Scale (HRS) and the Mystical Experience Questionnaire (MEQ30) after the dosing session. We found that higher psychedelic effects measured by both HRS and MEQ30 correlated with improvements in clinical outcome at D7. Finally, to investigate the neural bases of the antidepressant effects of ayahuasca, we used fMRI data through an emotional and resting state protocols at baseline, and one day after dosing. We observed changes in key limbic regions, such as subgenual cingulate cortex, amygdala and insula in ayahuasca group when compared to placebo. To our knowledge this is the first controlled trial to test a psychedelic substance in treatment resistant depression. Overall, this study brings new evidence supporting the safety and therapeutic value of ayahuasca, dosed within an appropriate setting, to help treat depression.

6
  • DANIELA MARIA DE SOUSA MOURA
  • Alterations in the cell lineage and neuronal organization in the adult dentate gyrus in two animal models of epilepsy

  • Leader : MARCOS ROMUALDO COSTA
  • MEMBRES DE LA BANQUE :
  • MARCOS ROMUALDO COSTA
  • CECILIA HEDIN PEREIRA
  • DIEGO ANDRES LAPLAGNE
  • EMELIE KATARINA SVAHN LEAO
  • GABRIEL MAISONNAVE ARISI
  • Data: 30 août 2017


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  • The granular cells of the hippocampus are one of the few types of neurons generated in the central nervous system of adult mammals. The current model of neurogenesis in the adult hippocampus assumes that neural stem cells (NSCs) give rise to progenitors restricted to the generation of neurons or astrocytes. Environmental stimuli and pathological conditions can alter the lineage progression, modulating cell proliferation, differentiation, survival and synaptic integration of newly generated neurons. For example, mesial Temporal Lobe Epilepsy (mTLE), the most common form of epilepsy in adults, is associated with changes in the rate of adult hippocampal neurogenesis. In this work, we used two experimental mTLE models to evaluate the effects of an epileptogenic insult (i.e., status epilepticus, SE) on the cell lineage and neuronal maturation in the adult dentate gyrus. Using Dcx-CreERT2 / CAG-CAT-GFP animals, we fate mapped the fate of cells expressing the doublecortin gene (DCX) either before or after intrahippocampal injection of the convulsive agents kainic acid or pilocarpine. In this way, we could evaluate the effect of these drugs on DCX+ progenitors and immature neurons generated before or after treatment. In both models, we observed an increase of neurogenesis and changes in the positioning and morphology of granular cells, according to previous descriptions in the literature. Neuronal aberrations, such as ectopic localization and presence of basal dendrites, were observed both in cells generated before and after induction of ES, albeit at different frequencies. However, only in the hippocampus ipsilateral to the injection of kainic acid we observed granule cell dispersion and neuronal death in CA1 and CA3, although the paroxysmal epileptic activity occurred in both hippocampi. Surprisingly, the increase of neurogenesis in animals that received kainic acid was restricted to the contralateral hippocampus, whereas on the ipsilateral side a significant increase in astrocyte generation was observed within the DCX+ progenitor lineage. In addition, we also observed the presence of cells with NSC hallmarks, suggesting that DCX+ progenitors could regress to more primitive states in the adult hippocampal cell lineage. The increased astrogliogenesis on the ipsilateral side to the injection of kainic acid was associated with a degeneration of parvalbumin (PV)+ interneurons in the hippocampus, suggesting that GABAergic activity could be contributing to the rerouting of the DCX+ progenitor cell lineage. Taken together, our data indicate that the cell lineage in the dentate gyrus is neither unidirectional nor irreversible, and that the increased neuronal electrical activity induced by kainic acid and pilocarpine have different effects on cell differentiation and the fate of progenitors and neurons in that region. These results highlight the need to review the current model of adult hippocampal neurogenesis and also indicate that different animal models of epilepsy produce distinct cellular alterations in the adult hippocampus and could therefore represent different degrees / stages of the pathology.

2016
Thèses
1
  • RAFAELA FAUSTINO LACERDA DE SOUZA
  • Influência da postura da mão na identificação da lateralidade: uma análise eletrofisiológica

  • Leader : ANTONIO PEREIRA JUNIOR
  • MEMBRES DE LA BANQUE :
  • DRAULIO BARROS DE ARAUJO
  • ALLAN PABLO DO NASCIMENTO LIMEIRA
  • ANTONIO PEREIRA JUNIOR
  • Data: 28 avr. 2016


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  • Estudos recentes têm demonstrado que o reconhecimento da lateralidade de mãos em uma perspectiva de segunda pessoa engaja processos de imagética motora. No entanto, pouco se sabe sobre a atividade e contribuição das regiões sensório-motoras corticais nesse processo. O objetivo do presente estudo é mostrar como a rotação mental de estímulos visuais de partes do corpo influenciam o processamento neural dessas regiões através da modulação da atividade oscilatória de grupos neuronais nas faixas alfa e beta. Para tanto, realizamos a análise da perturbação espectral relacionada ao evento (ERSP) do registro eletroencefalográfico (EEG) de 20 sujeitos engajados no reconhecimento da lateralidade de mãos apresentadas em uma tela de computador. Os resultados mostram que a supressão da amplitude das frequências alfa e beta foi maior nas regiões sensório-motoras e que características do estímulo (como orientação da mão, visão, postura de dedos e lateralidade) são capazes de modular esses componentes oscilatórios em diferentes regiões, sugerindo etapas distintas para o processamento da tarefa cognitiva.

2
  • JOSEPH ANDREWS BELO ALVES
  • Coordination of sensorimotor rhythms during rat exploratory behavior

  • Leader : DIEGO ANDRES LAPLAGNE
  • MEMBRES DE LA BANQUE :
  • DIEGO ANDRES LAPLAGNE
  • FLAVIO FREITAS BARBOSA
  • ADRIANO BRETANHA LOPES TORT
  • Data: 17 août 2016


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  • When actively exploring the environment, rats exhibit several rhythmic behaviors with frequencies in the theta Range (5-10 Hz). These include sniffing (active fast respiration), whisking (movement of the facial vibrissae), and ultrasonic vocalizations. Synchronizations between each pair of these behaviors have been observed in recent studies: vibrissae protraction-retraction is linked to the inhalation-exhalation phase of breathing; constriction of the vocal folds for vocalization, in turn, is locked to the exhalation phase of sniffing; accordingly, vocalizations were observed to synchronize with the retraction phase of whisking. These and other observations point to an interaction of rhythm and pattern generators in the brainstem controlling the coordination of respiratory, oral and facial movements. To better understand the hierarchies among these circuits we simultaneously recorded sniffing, whisking and vocalizations from rats during free social exploration. For this purpose, eight electrodes were inserted surgically to acquire bilateral EMG signals from muscles controlling the protraction and retraction of the whiskers and a cannula was implanted through the nasal bone to record the respiratory cycle. After one week of recovery and habituation, two rats (one implanted and one naive) were placed across a gap where they could explore each other. These interactions were filmed with a high speed camera (250 Hz) to capture whisker movements and ultrasonic vocalizations were recorded from an overhanging microphone. We made frequency and phase analysis to validate the recorded signals and characterize the interplay between these sensorimotor rhythms. Results confirmed that both sniffing and whisking occur in bouts at theta frequencies during social exploration. Furthermore, we observed the expected anti-phase relationship between the EMGs from muscles controlling whisker protraction and retraction as well as their tight synchrony with the sniffing cycle. Interestingly, our data suggests that this synchrony is immediately lost during the emission of ultrasonic vocalizations. Instead, we observed a novel whisking behavior, consisting of active vibrissae protraction and retraction independent of the respiratory cycle.

3
  • RAFAEL DOS SANTOS DE BESSA
  • Dynamics of status epilepticus in two animal models of temporal lobe epilepsy

  • Leader : RODRIGO NEVES ROMCY PEREIRA
  • MEMBRES DE LA BANQUE :
  • HINDIAEL AERAF BELCHIOR
  • JOAO PEREIRA LEITE
  • CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
  • RODRIGO NEVES ROMCY PEREIRA
  • Data: 30 août 2016


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  • Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults. It is characterized by a progressive occurrence of epileptic seizures originating in the temporal lobe, particularly in the hippocampal formation (mesial TLE). Among the animal models used to investigate the physiopathological mechanisms of TLE, the most used are those that lead to spontaneous seizures after an initial insult, such as a prolonged convulsive state (status epilepticus, SE). This condition can be induced by the administration of the glutamatergic agonist, kainic acid (KA) or the cholinergic agonist, pilocarpine (PILO). However, the use of systemic injections and the lack of electrophysiological monitoring during SE lead to high mortality rates, widespread cell death and high behavioral variability during the chronic phase of epilepsy, which differs in several aspects from the human condition. These effects are mainly due to the lack of electrographic control of SE duration and the dynamics of the epileptogenesis process during the weeks following SE. Therefore, this project aimed to generate two animal models of TLE by intra-hippocampal injections of KA or PILO, and then, to analyze their behavioral and electrographic progression during SE. It is important to notice that no electrophysiological study has investigated the SE dynamics in animals infused with PILO into hippocampus so far. For that, we implanted two bundles of microelectrodes in the hippocampus bilaterally, one bundle in the medial prefrontal cortex and a cannula above the intermediate hippocampus for KA or PILO infusion. Following SE induction, we analyzed the behavioral and electrophysiological evolution of KA and PILO animals. SE was blocked after 2h by the injection of an anti-convulsant cocktail and the animals were continuously monitored by video-EEG for up to 72h. Seven days after SE, animals underwent euthanasia and had the brains removed for histological localization of cannula and electrodes. Video and EEG recordings were analyzed by visual inspection and spectral decomposition. Our results showed that PILO animals had shorter latency for first behavioral seizure than KA rats after drug injection. However, seizure severity showed higher variability among PILO rats (PILO: 50% animals had class 3 or higher vs.KA: 90% animals had class 1; Racine’s scale). PILO animals had a reduced number of wet-dog shake behaviors and shorter latency to SE onset as compared to KA rats. Electrophysiologically, we observed that high frequency oscillations (>150 Hz) occurred short after the injection of both drugs (15-40min before SE onset), as opposed to what is commonly reported to occur during the chronic phase of epilepsy in rodents. They were usually found within the first electrographic seizures. Finally, we have identified a distinct modular organization of paroxystic activity during the SE in each group, which consisted of blocks of nested rhythms. These findings thus suggest that PILO is more epileptogenic that KA and that these drugs produce distinct SE dynamics, which seem to be organized as periodically repeating modules of nested oscillations, modules of hypersynchrony with no nested oscillations and segments of asynchronous activity. Our data emphasizes the importance to conduct electrophysiological recordings during SE induction in order to better control individual brain responses. This can reduce variability during epileptogenesis and produce a more homogeneous model of chronic epilepsy.

4
  • RAFAEL FRANZON BENZ
  • Salicylate generates anxiety-like behavior and type 2 theta oscillation in the ventral hippocampus of mice

  • Leader : RICHARDSON NAVES LEAO
  • MEMBRES DE LA BANQUE :
  • RICHARDSON NAVES LEAO
  • GEORGE CARLOS DO NASCIMENTO
  • RICARDO MAURÍCIO XAVIER LEÃO
  • Data: 20 sept. 2016


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  • Salicylate, the main compound of many medications as Aspirin, is known to cause tinnitus if consumed in high doses or in a chronic way (for the treatment of osteoporosis, for example). Tinnitus is the hearing or perception of a sound when no physical stimulus is present. Tinnitus is not a disease itself, but a symptom present in some diseases, and is associated with anxiety and other mood disorders. Despite being directly related with auditory system, tinnitus is not generated from one specific region of the brain. Additionally, some studies showed that salicylate affects various brain regions besides the auditory system, as the striatum, amygdala and the hippocampus. Early studies have ascribed a unitary function to the hippocampus: declarative memory processing. However, more recent studies showed that the hippocampus not only has other functions, as emotional processing, but also can be divided into ventral and dorsal, and the ventral part plays an essential role in emotional processing. The most studied oscillation of the brain is the theta rhythm, and it can be found in the entire hippocampus. Two types of theta can be distinguished: the type 1, that is atropine resistant, has a higher frequency (7 to 10 Hz) and is related with motor pattern behaviors; and the type 2 theta, that is atropine sensitive, has a lower frequency (5 to 7 Hz) and occur during anesthesia, alert immobility and high arousal situations. The present study investigated the electrophysiological effects of salicylate in the ventral hippocampus of behaving mice. Through salicylate injection we generated type 2 theta in the ventral hippocampus. We also found that salicylate led to anxiety-like behavior. 

5
  • SYLVIA GALVÃO DE VASCONCELOS PINHEIRO
  • SpeechGraph Analysis of literary texts: Investigation of psychotic traits

  • Leader : SIDARTA TOLLENDAL GOMES RIBEIRO
  • MEMBRES DE LA BANQUE :
  • ALVARO JOSE MAGALHÃES DE QUEIROZ
  • SIDARTA TOLLENDAL GOMES RIBEIRO
  • CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
  • MAURO COPELLI
  • Data: 30 sept. 2016


  • Afficher le Résumé
  • Recent studies in computational psychiatry (Mota et al., 2012, Mota et al., 2014, Mota et al., in preparation) indicate significant structural differences between the speech of psychotic and healthy subjects. Graph analysis of these subjects’ autobiographic reports allow the quantification of psychotic speech symptoms, marked by poor, disconnected and repetitive speech. In the 1970’s, Julian Jaynes proposed that psychosis was socially prevalent until around 1,000 BC. This conjecture was first tested by Diuk et al. (2012), who used Latent Semantic Analysis to assess the semantic similarity to the introspection concept across Judeo-Christian and Greco-Roman texts from the first millenium BC. In this perspective, we seek to investigate this hypothesis proceeding graph analysis of 448 texts across history, from 3,000 BC to 2,010 AC. Graph measures of six different cultures of Afro-Eurasia (Syro-Mesopotamian, Egyptian, Hindu, Persian, Judeo-Christian, Greek-Roman) and three more recent literary categories (Medieval, Modern, and Contemporary) reveal a clear pattern: While lexical diversity and connectivity increase, recurrence decreases. These findings are compatible with the notion that psychosis is an early trait of our species.

Thèses
1
  • TIAGO SIEBERT ALTAVINI
  • A influência das conexões inter-hemisféricas em mapas de preferência de orientação espontâneos e evocada e nas atividade de spiking

  • Leader : KERSTIN ERIKA SCHMIDT
  • MEMBRES DE LA BANQUE :
  • SERGIO TULIO NEUENSCHWANDER MACIEL
  • ADRIANO BRETANHA LOPES TORT
  • BRUSS REBOUÇAS COELHO LIMA
  • JEROME PAUL ARMAND LAURENT BARON
  • KERSTIN ERIKA SCHMIDT
  • Data: 29 janv. 2016


  • Afficher le Résumé
  • A atividade cerebral espontânea exibe padrões que lembram o de coativação de conjuntos neuronais em resposta a estímulos ou tarefas. Estes padrões tem sido atribuídos a arquitetura funcional do cérebro, e.g. conexões de longo alcance em patches (manchas, fragmentos). Nós investigamos diretamente a contribuição destas conexões em patches entre hemisférios para mapas espontâneos e evocados na área 18 próxima a borda 17/18 de gatos. Registramos mapas com imageamento por votage-sensitive dye (VSD) e atividade despiking enquanto manipulamos o input interhemisférico pela desativação reversível das áreas correspondentes contralaterais. Durante a desativação os mapas espontâneos continuaram sendo gerados com frequência e qualidade semelhante ao da rede intacta, mas um viés de orientações cardinais desapareceu. Neurônios com preferência por orientações horizontais (HN) ou verticais (VN), ao contrário dos de preferência oblíqua, diminuiram sua atividade de repouso, no entanto, HN tiveram a atividade diminuída mesmo quando estimulados visualmente. Concluímos que mapas espontâneos estruturados são primariamente gerados por conexões tálamo- e/ou intracorticais. Entretanto, conexões de longo alcance pelo corpo caloso - como um prolongamento da rede de longo alcance intracortical - contribui para um viés cardinal, possivelmente porque estas conexões são mais fortes ou mais frequentes entre neurônios preferindo orientações horizontais e/ou cardinais. Estes contornos são mais fáceis de perceber e aparecem com mais frequência no ambiente natural, cone xões de longo alcance podem prover o córtex visual com um grid de operações probabilísticas de agrupamento em uma cena visual maior.
     
2
  • MALEK CHOUCHANE
  • REPROGRAMMING OF DISTINCT ASTROGLIAL POPULATIONS INTO SPECIFIC NEURONAL SUBTYPES IN VITRO AND IN VIVO

  • Leader : MARCOS ROMUALDO COSTA
  • MEMBRES DE LA BANQUE :
  • SANDRO JOSE DE SOUZA
  • CECILIA HEDIN PEREIRA
  • EMELIE KATARINA SVAHN LEAO
  • MARCOS ROMUALDO COSTA
  • RICARDO AUGUSTO DE MELO REIS
  • Data: 29 févr. 2016


  • Afficher le Résumé
  • Recently, the field of cellular reprogramming has been revolutionized by works showing the potential to directly lineage-reprogram somatic cells into neurons upon overexpression of specific transcription factors. This technique offers a promising strategy to study the molecular mechanisms of neuronal specification, identify potential therapeutic targets for neurological diseases and eventually repair the central nervous system damaged by neurological conditions. Notably, studies with cortical astroglia revealed the high potential of these cells to reprogram into neurons using a single neuronal transcription factor. However, it remains unknown whether astroglia isolated from different regions of the central nervous system have the same neurogenic potential and generate induced neurons (iN) with similar phenotypes. Similarly, little is known about the fate that iNs could adopt after transplantation in the brain of host animals. In this study we compare the potential to reprogram astroglial cells isolated from the postnatal cerebral cortex and cerebellum into iNs both in vitro and in vivo using the proneural transcription factors Neurogenin-2 (Neurog2) and Achaete scute homolog-1 (Ascl1). Our results indicate cerebellar astroglia can be reprogrammed into induced neurons (iNs) with similar efficiencies to cerebral cortex astroglia. Notably however, while iNs in vitro adopt fates reminiscent of cortical or cerebellar neurons depending on the astroglial population used for reprogramming, in situ, after transplantation in the postnatal and adult mouse brain, iNs adopt fates compatible with the region of integration. Thus, our data suggest that the origin of the astroglial population used for lineage-reprogramming affects the fate of iNs in vitro, but this imprinting can be overridden by environmental cues after grafting.

     

3
  • ROBSON SCHEFFER TEIXEIRA
  • *

  • Leader : ADRIANO BRETANHA LOPES TORT
  • MEMBRES DE LA BANQUE :
  • SERGIO TULIO NEUENSCHWANDER MACIEL
  • PABLO JOSE FUENTEALBA DURAND
  • OLAVO BOHRER AMARAL
  • DIEGO ANDRES LAPLAGNE
  • ADRIANO BRETANHA LOPES TORT
  • Data: 7 avr. 2016


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  • *

4
  • ANDERSON HENRIQUE FRANÇA FIGUEREDO LEÃO
  • RATOS ESPONTANEAMENTE HIPERTENSOS (SHR) SÃO RESILIENTES A UM MODELO ANIMAL PROGRESSIVO DA DOENÇA DE PARKINSON: UM ESTUDO NEUROQUÍMICO E COMPORTAMENTAL

  • Leader : REGINA HELENA DA SILVA
  • MEMBRES DE LA BANQUE :
  • REGINA HELENA DA SILVA
  • RUI DANIEL SCHRODER PREDIGER
  • JEFERSON DE SOUZA CAVALCANTE
  • CLAUDIO DA CUNHA
  • RODRIGO NEVES ROMCY PEREIRA
  • Data: 6 mai 2016


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  • A Doença de Parkinson (DP) é um distúrbio motor relacionado ao envelhecimento que atualmente acomete de 1-2% da população mundial acima dos 60 anos. No Brasil, estima-se que esta acometa aproximadamente 600 mil indivíduos, configurando-se como uma enfermidade de importância para países em processo de incremento da expectativa de vida. A epidemiologia da DP revela fatores de risco intrínsecos e extrínsecos ao paciente que definem a chance de desenvolvimento do distúrbio. Mutações pontuais e polimorfismos com significado funcional são tidos como fatores genéticos predisponentes, enquanto a exposição a pesticidas e toxinas destacam-se como fatores ambientais. No entanto, poucos estudos em modelos animais focam em investigar a interação entre estes fatores. Isto pode ser alcançado comparando-se os efeitos de substâncias indutoras de parkinsonismo em linhagens de ratos com diferentes contextos genéticos. Recentemente, o tratamento repetido com baixas doses de reserpina – um inibidor irreversível do transportador vesicular de monoaminas (VMAT2) – foi proposto como um modelo progressivo para a DP. Sob este regime de tratamento, roedores apresentam, de forma progressiva, comprometimento motor, cognitivo, e alterações neuroquímicas compatíveis com a fisiopatologia da DP. Em paralelo, comparados a ratos Wistar, animais da linhagem SHR (Spontaneously Hypertensive Rats) são resistentes à indução da discinesia oral pelo tratamento agudo com reserpina. Em vista destes achados, nós buscamos avaliar se ratos SHR seriam resistentes aos déficits motores e alterações neuroquímicas quando submetidos ao modelo progressivo para DP induzido por reserpina. Portanto, nós submetemos ratos Wistar e SHR ao tratamento agudo (1 mg/kg) ou repetido (15 injeções de 0,1 mg/kg, em dias alternados) com reserpina e investigamos a progressão dos déficits motores nas tarefas de catalepsia em barra, discinesia oral, e atividade espontânea em campo aberto. Observamos então que, para ambos os regimes de tratamento, animais SHR se mostram resilientes ao prejuízo motor em todas as dimensões motoras avaliadas. Ainda, estas diferenças se manifestaram tanto na latência para o surgimento do comprometimento motor como para a magnitude deste. Estas alterações foram ainda acompanhadas por decréscimo na expressão da tirosina hidroxilase (TH) e incremento na expressão de α-sinucleína na via nigro-estriatal de ambas linhagens submetidas ao tratamento com reserpina. Estas alterações neuroquímicas resultantes do tratamento com reserpina também se refletiram nos níveis de monoaminas – dopamina e serotonina – na via nigro-estriatal destes animais. De modo geral, como no comportamento motor, animais SHR apresentaram atraso para a depleção de monoaminas e menor magnitude deste efeito. Em conclusão, os resultados aqui apresentados claramente corroboram a resiliência de ratos SHR ao modelo progressivo da DP. Estes achados expõem novos alvos potenciais para as diferenças neuroquímicas, moleculares e genéticas na linhagem SHR relevantes para o estudo da susceptibilidade à DP.

5
  • ARTHUR SÉRGIO CAVALCANTI DE FRANÇA
  • The role of beta2 oscillations and OLMα2 interneurons in the CA1 region of the mouse hippocampus in object recognition memory

  • Leader : ADRIANO BRETANHA LOPES TORT
  • MEMBRES DE LA BANQUE :
  • JANINE INEZ ROSSATO
  • CLAUDIO DA CUNHA
  • FLAVIO FREITAS BARBOSA
  • DIEGO ANDRES LAPLAGNE
  • ADRIANO BRETANHA LOPES TORT
  • Data: 4 oct. 2016


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  • The hippocampus is associated to novelty detection and formation of explicit memories. The present work aims at better understanding the role of the CA1 region of the hippocampus in these processes. By employing electrophysiology, animal behavior, psychopharmacology and optogenetic techniques in transgenic and wild-type mice, we found that CA1 OLMα2 cells influence the formation of new object representations in an object recognition task, as well as the encoding of aversive memories in a contextual fear memory task. Furthermore, we characterized a new oscillatory activity in the local field potential of CA1 at beta 2 frequency (23-30 Hz), which was typically transient and linked to the amount of novelty in an object recognition task. These results suggest potential cellular and network mechanisms that underlie the role of CA1 in memory formation and novelty detection.

6
  • MARKUS MICHAEL HILSCHER
  • Synchronization by Distal Dendrite-targeting Interneurons

  • Leader : EMELIE KATARINA SVAHN LEAO
  • MEMBRES DE LA BANQUE :
  • EMELIE KATARINA SVAHN LEAO
  • MARTIN PABLO CAMMAROTA
  • KERSTIN ERIKA SCHMIDT
  • GILAD SILBERBERG
  • CHRISTOPHER KUSHMERICK
  • Data: 1 déc. 2016


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  • Synchronization among neurons arises from the cooperative interaction of various cell types through excitation and inhibition. The mechanisms behind this type of neuronal coordination are as versatile as almost no other coordination task in the brain, making its comprehension heavily challenging. Among many others, the high number of involved cell types, the diversity of synaptic processes as well as the contribution of a multitude of ion channels and currents span the plurality of neuronal synchronization mechanisms in our brains. Focusing on two main brain areas, the hippocampus and the cortex, this thesis aims to understand the role of distal dendritetargeting interneurons in shaping pyramidal cell activity and the timing of their action potentials.

    The distribution of ion channels and synaptic receptors in pyramidal cell dendrites is extremely anisotropic. Thus, interneurons innervating the proximal or distal areas of the dendrites cause different effects in the target cell when activated. For example, the distal portions of the pyramidal cell dendrites contain one of the most prominent pacemaker channels: the hyperpolarizationactivated cyclic nucleotide-gated channels. These channels produce a cationic depolarizing current (Ih) and play an important role in the regulation of neuronal excitability. Using computational modeling, this thesis shows how the amount of Ih in certain cell types changes their spike rate, synchrony as well as power and frequency of ongoing network oscillations. Moreover, since Ih differs between brain regions as well as cell types and location, this thesis electrophysiologically explores how Ih differs along the dorso-ventral axis of hippocampus in oriens-lacunosum moleculare (OLM) cells, the main distal dendrite-targeting interneurons of that region.

    Utilizing the main distal dendrite-targeting interneuron of the cortex, the Martinotti cell, this thesis also shows how a defined population of interneurons can be manipulated in order to control and align pyramidal cell firing. By providing the right amount and frequency of inhibition, Martinotti cells are able to synchronize trains of subtype-specific pyramidal cells. Using optogenetic approaches to activate/inactivate populations of Martinotti cells, these dendrite-targeting interneurons are shown to trigger rebound action potentials in pyramidal cells when temporally
    aligned. The rebound action potentials in turn are the result of strong Martinotti cell inhibition, giving these distal dendrite-targeting interneurons the potential to reset pyramidal cell firing.

    Overall, Martinotti cells and OLM cells show quite striking similarities in morphological, neurochemical and electrophysiological properties. Especially, their long axonal projections to upper layers as well as their low-threshold, slow spiking fashion and the accommodating firing make these distal dendrite-targeting interneurons so special for neuronal synchronization

2015
Thèses
1
  • JOSÉ HENRIQUE TARGINO DIAS GÓIS
  • EFEITOS DA NICOTINA NO COMPLEXO DO SEPTO MEDIAL NA VIA SEPTO HIPOCAMPAL EM CAMUNDONGOS ANESTESIADOS POR KETAMINA

  • Leader : RICHARDSON NAVES LEAO
  • MEMBRES DE LA BANQUE :
  • WILFREDO BLANCO FIGUEROLA
  • RICHARDSON NAVES LEAO
  • GEORGE CARLOS DO NASCIMENTO
  • Data: 24 févr. 2015


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  • The hippocampus is known to be crucial to mammals to create new memories; the MS/DBB is the major hippocampal cholinergic input. Early electrophysiological studies proposed MS/DBB as the key structure to theta rhythmogenesis. It has been demonstrated in the literature that nicotine can induce theta rhythm in vitro on both structures. This work investigates the role of nicotine in the MS/DBB on the septo-hippocampal pathway rhythmogenesis in ketamine-anaesthetised mice. My in vivo experiments showed that, although microinfusions of nicotine in the MS/DBB didn’t elicit theta rhythm in either structure, it induced gamma rhythm on both. This increase of gamma can be an electrophysiological substrate to the enhancement on attention reported in psychophysical experiments.

    The literature reports that nicotine on MS/DBB depolarizes local glutamatergic neurons to excite both local and projection GABAergic neurons; and that the generation of gamma can be a result of a local network and modulated by conductance of GABA receptors. My experiments corroborates with the current hypothesis of gamma oscillation genesis. Although not present, nicotine-induced theta rhythm couldn’t be observed because of the ketamine-induced delta rhythm. A realistic model implementing known currents – with Hodgkin-Huxley formalism – of the three major neuron types of MS/DBB replicated the gamma oscillation seen in the experiments, higher excitability on glutamatergic neurons would elicit a higher power within gamma rhythm frequency band. In my in vitro experiments, I couldn’t find a neuron that would fire on these findings, supposedly because the lack of afferents that leads the network to a less excited state.

2
  • BRYAN DA COSTA SOUZA
  • Caracterização de células de lugar no hipocampo e de suas relações com oscilações do potencial de campo local.
     

  • Leader : ADRIANO BRETANHA LOPES TORT
  • MEMBRES DE LA BANQUE :
  • OLAVO BOHRER AMARAL
  • ADRIANO BRETANHA LOPES TORT
  • DIEGO ANDRES LAPLAGNE
  • Data: 13 mars 2015


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  • As principais vias aferentes ao hipocampo vêm do córtex entorrinal e fazem parte de um loop que retorna ao entorrinal após passar pelo giro denteado, e pelas subareas do hipocampo CA3 e CA1. Desde a descoberta nos anos 50 de que o hipocampo está envolvido na formação de memórias, esta região vem sendo extensivamente estudada. Além desta função mnemônica, o hipocampo também está associado a navegação espacial. Em camundongos e ratos, células de lugar exibem um aumento da taxa de disparo relacionado à posição do animal. O local do ambiente onde uma determinada célula de lugar se ativa é chamado de campo de lugar. A taxa de disparo das células de lugar é máxima quando o animal está no centro do campo de lugar, e diminui a medida que ele se afasta desse ponto, sugerindo a existência de uma codificação espacial baseada em taxa de disparos. Entretanto, pesquisas prévias vêm mostrando a existência de oscilações hipocampais em múltiplas frequências e ligadas a diferentes estados comportamentais, e muitos acreditam que estas oscilações são importantes para uma codificação temporal. Em particular, oscilações teta (5-12 Hz) possuem uma relação espaço-temporal com as células de lugar conhecida como precessão de fase. Na precessão, a fase de disparos da célula de lugar muda gradualmente do pico de teta para o fundo e, posteriormente, para a fase ascendente, a medida que o animal atravessa o campo de lugar. Além disso, as teorias vigentes sugerem que CA1, a porta de saída do hipocampo, intermediaria a comunicação com o córtex entorrinal e CA3 através de oscilações em diferentes frequências chamadas, respectivamente, de gama alto (60-100 Hz; HG) e gama baixo (30-60 Hz; LG). Essas oscilações se relacionam com teta, estando aninhadas dentro de cada ciclo desta frequência mais lenta. Nesta dissertação, utilizamos dados disponibilizados online para fazer análises computacionais visando reproduzir resultados clássicos e recentes acerca da atividade das células de lugar no hipocampo de ratos em livre movimento. Em particular, nós revisitamos o debate sobre a relação da precessão de fase com variações na taxa de disparos e na posição do animal no campo de lugar. Concluímos que este fenômeno não pode ser explicado por nenhuma dessas variáveis sozinha, e sim pela interação entre elas. Nós também realizamos novas análises investigando as propriedades das células de lugar em relação às oscilações. Nós mostramos que o nível de modulação dos disparos por teta afeta apenas levemente a informação espacial contida nas células de lugar, enquanto a fase de disparo média não tem nenhuma influência na informação espacial. Também encontramos que as células de lugar estão moduladas por teta quando disparam fora do campo de lugar. Além disso, nossos resultados mostram que o disparo das células de lugar dentro do ciclo de teta segue os padrões de modulação de HG e LG por teta presentes nos potenciais de campo local de CA1 e córtex entorrinal. Por último, achamos um acoplamento fase-amplitude em CA1 associado apenas aos disparos dentro do campo de lugar na faixa de 40-80 Hz. Concluímos que o disparo de células de lugar está ligado a estados de rede refletidos no potencial de campo local e sugerimos que a atividade dessas células sejam interpretadas como um estado dinâmico ao invés de uma propriedade fixa da célula.

     


3
  • JÉSSICA ALVES DE MEDEIROS ARAÚJO
  • "REPROGRAMAÇÃO DE CÉLULAS-TRONCO MESENQUIMAIS EM NEURÔNIOS UTILIZANDO GENES PRÓ-NEURAIS"

     

  • Leader : MARCOS ROMUALDO COSTA
  • MEMBRES DE LA BANQUE :
  • EMELIE KATARINA SVAHN LEAO
  • STEVENS KASTRUP REHEN
  • MARCOS ROMUALDO COSTA
  • Data: 8 avr. 2015


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  • A possibilidade de repor células perdidas em doenças neurodegenerativas através de transplantes com células-troncos das mais diversas fontes vem sendo amplamente estudada. As células-tronco adultas (CTA) podem ser facilmente isoladas e sua utilização na pesquisa não envolve questões éticas e religiosas. Além disso, estas células são menos propícias à transformação tumoral do que células-tronco embrionárias, outra importante fonte de células para terapias celulares. No entanto, as CTA são, em estados fisiológicos, restritas a geração de células dos seus tecidos de origem, o que poderia limitar a sua utilização. Porém, nos últimos anos, uma série de técnicas vem sendo descritas com o objetivo de reverter tais limitações. Neste trabalho, nós investigamos a capacidade das células-tronco mesenquimais, isoladas de camundongos adultos ou do cordão umbilical humano adulto, serem induzidas a adquirir um fenótipo neuronal de forma direta, sem passar por um estágio de célula progenitora ou pluripotente, através da reprogramação genética com genes pró-neurais. Nossos resultados indicam que tanto células-tronco mesenquimais adultas murinas quanto humanas podem ser reprogramadas em neurônios após a expressão combinada de Sox2 e Ascl1 ou Sox2 e Neurog2. As células reprogramadas exibem morfologias compatíveis com o fenótipo neuronal, expressam proteínas típicas de neurônios maduros, apresentam a capacidade de gerar potenciais de ação repetitivos e formam conecções sinápticas com outros neurônios presentes no cultivo. Portanto, nosso trabalho apresenta a primeira evidência de reprogramação direta de células-tronco mesenquimais humanas em neurônios funcionais.

4
  • LUANA GABRIELLE DE FRANÇA FERREIRA
  • Influência do Jet lag social em marcadores circadianos de atividade - repouso e cardíaco em estudantes de medicina.

  • Leader : JOHN FONTENELE ARAUJO
  • MEMBRES DE LA BANQUE :
  • SIONALDO EDUARDO FERREIRA
  • JOHN FONTENELE ARAUJO
  • SIDARTA TOLLENDAL GOMES RIBEIRO
  • Data: 10 avr. 2015


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  • Os estudos revelam que nas ultimas décadas ocorreu uma diminuição na duração do sono.  Os compromissos sociais, como o trabalho e a escola, muitas vezes não estão alinhados ao “tempo biológico” dos indivíduos. Somado a isso, observa se uma menor força do zeitgeber causada pela menor exposição à luz de dia e maior à noite. Isso gera um débito de sono crônico que é compensado nos dias livres ocorrendo semanalmente uma restrição e extensão do sono denominada de Jet lag social. A privação de sono vem sendo associada à obesidade, risco cancerígeno e cardiovascular. Sugere-se que o sistema nervoso autonômico seja um caminho que relaciona os problemas do sono às doenças cardiovasculares. No entanto, além das evidências demonstradas por pesquisas com uso de modelos de privação de sono de forma aguda e controlada, são necessários estudos investigando efeitos da privação do sono de forma crônica como ocorre no Jet lag social. O objetivo deste estudo foi investigar a influência do Jet lag social em marcadores circadianos de atividade-repouso e cardíacos em estudantes de medicina. Trata-se de um estudo transversal e observacional realizado no departamento de fisiologia pelo Laboratório de Neurobiologia e Ritmicidade Biológica (LNRB) da UFRN. Participaram da pesquisa estudantes de medicina matriculados no 1º período do curso da UFRN. Foram utilizados os seguintes instrumentos: Questionário Cronotipo de Munique (MCTQ); Questionário para identificação de indivíduos matutinos e vespertinos (MEQ ou HO); Índice de qualidade do sono de Pittsburgh; Escala de Sonolência de Epworth; Actímetro; Cardiofrequencímetro. Foram analisadas variáveis de caracterização do sono, não paramétricas (IV60, IS60, L5 e M10) e índices cardíacos no domínio do tempo (intervalo RR, FC, SDNN, RMSSD, STD HR, NN50, pNN50), frequência (LF, HF, LF/HF) e não linear (SD1, SD2, SD1/SD2). Realizou-se análise estatística descritiva, comparativa e correlação com uso do programa SPSS versão 20. Participaram do estudo 41 estudantes, 48,8% (20) mulheres e 51,2% (21) homens, 19,63 ± 2,07 anos. O Jet lag social teve uma média de 02:39h ± 00:55h, 82,9% (34) com Jet lag social ≥ 1 hora e houve correlação negativa com escore cronotipo de Munique evidenciando maior privação do sono em indivíduos com tendência à vespertinidade. 90,2% (37) tiveram qualidade do sono ruim (X2 = 26,56, p < 0,001) e 56,1% (23) sonolência diurna excessiva (X2 = 0,61, p = 0,435). Observou-se diferença significativa dos valores de LFnu, HFnu e LF/HF entre os grupos de Jet lag social < 2h e ≥ 2h e houve correlação do Jet lag social com LFnu (rs = 0,354, p = 0,023), HFnu (rs = - 0,354, p = 0,023) e LF/HF (rs = 0,355, p = 0,023). Verificou-se ainda associação negativa entre IV60 e índices no domínio do tempo e não lineares. Sugere-se que a privação crônica de sono pode ter associação com maior atividade simpática promovendo maior risco cardiovascular.

5
  • THAWANN MALFATTI BORGES
  • VALIDATION OF OPTOGENETIC PROTEIN EXPRESSION IN THE DORSAL COCHLEAR NUCLEUS – MOLECULAR BASIS FOR IN VITRO AND IN VIVO INVESTIGATION OF TINNITUS IN MICE

     

     

     

  • Leader : EMELIE KATARINA SVAHN LEAO
  • MEMBRES DE LA BANQUE :
  • EMELIE KATARINA SVAHN LEAO
  • RICHARDSON NAVES LEAO
  • RICARDO MAURÍCIO XAVIER LEÃO
  • Data: 26 juin 2015


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  •  

    Tinnitus is the perception of a sound in the absence of a corresponding physical stimulus. It is not clear yet what mechanisms are involved in tinnitus and how it starts and/or becomes chronic. Due to the relationship between tinnitus and somatosensory trauma/stimuli, the dorsal cochlear nucleus (DCN), a region known to integrate somatosensory and auditory pathways, has been identified as a potential key structure in the generation of phantom sound perception. Here, we target specific neuronal populations in the DCN to allow further investigation on how this region may contribute to the generation of tinnitus signals that spread to other auditory areas. We examined the expression of optogenetic proteins (Channelrhodopsin 2 - ChR2; and enhanced Archaerhodopsin 3.0 - eArch3.0), targeting neurons expressing Calmoduline Kinase II alpha (CaMKIIa) promoter in wild-type C57/Bl6 mice and neurons expressing nicotinic acetylcholine receptor subunit alpha-2 promoter (ChRNA2) in ChRNA2- Cre transgenic C57/Bl6 mice, using local virus injection, verified by fluorescence microscopy. Unit responses were differentiated based on their electrophysiological response to sound. We then investigated if firing of neurons expressing optogenetic tools can be controlled in vivo and if the same neurons also fire action potentials in response to precisely timed sound stimulation. Both in vivo and preliminary in vitro data shows that neurons expressing ChR2 do respond to sound, and that they furthermore also can respond to light stimulation with a stable and similar waveform. Moreover, in vivo data shows that neurons expressing eArch3.0, responding to sound, will decrease their firing rate when exposed to green light. Thereby showing that optogenetic tools can be used functionally in the DCN, it is possible to further test tinnitus theories by, for example, producing an increased firing rate in the DCN, trying to mimic tinnitus; or inhibiting increased spontaneous firing rate in the DCN of animals with noise-induced or salycilate-induced tinnitus.


     

6
  • GIOVANNE DE ROSSO MANÇOS
  • Do fast retinal oscillations play a role in vision? a study in the anesthetized and awake cat

  • Leader : SERGIO TULIO NEUENSCHWANDER MACIEL
  • MEMBRES DE LA BANQUE :
  • JEROME PAUL ARMAND LAURENT BARON
  • CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
  • SERGIO TULIO NEUENSCHWANDER MACIEL
  • Data: 28 août 2015


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  • Early physiologists were dazzled by the occurrence of high-amplitude, periodic oscillations, easily discernible in recording traces from the eye, optic tract and optic ganglia. Numerous studies thereafter pointed to retinal ganglion cell as the elements responsible for the generation of these fast rhythms, which were known to propagate to the lateral geniculate and to the cortex. Only recently, however, these early observations gained renewed interest, mainly in the light of recent theories linking neuronal oscillations to various cognitive processes, such as perceptual binding, attention and memory. In this context, fast retinal oscillations (FRO) have been associated to the binding of contiguous contours or surfaces, which in principle could support a fast feedforward segmentation process. In addition, a series of experiments in the cat have shown that FRO may convey global stimulus properties, such as size.

    A limitation in these previous studies, however, was that most of them where were made in the anesthetized and paralyzed cat. Only a few early studies have been performed in the non-anesthetized but still paralyzed cat. Another concern was that, in these latter experiments, visual stimuli were often limited to ganzfeld flashes, far from natural vision conditions. Moreover, very recently we made the surprising discovery that FRO depend strongly on halothane (and isoflurane) anesthesia. It was therefore imperative to verify whether FRO are present or not in the awake cat, in naturalistic conditions, such as during free-viewing of a visual scene. This is the main goal of the present study.

    Simultaneous multiple-electrode recordings were made from the LGN and the retina of anesthetized cats (N= 3) and from the LGN of an awake cat (N= 1). Comparisons were made for responses to natural movies and flashed stationary light stimuli. To test specifically the role of FRO in encoding stimulus size we designed a protocol made of a light circle of varying size along the trial. Spike sorting techniques allowed us to study separately the ON- and OFF-components of the responses. Analysis consisted in measuring synchronous oscillations for single cell spiking activity in the time (sliding correlation analysis) and spectral domains (multitaper spectral analysis, multitaper coherence). Our present results based on single-cells extend our previous findings in the anesthetized cat, which were restricted to an autocorrelation analysis of LGN mutiunitary responses. Both ON- and OFF-responses to varying size stimuli show that coherent oscillations appear only after the stimulus attained a minimum size of about 5°, suggesting that FRO is rather limited in encoding subtle changes in stimulus size. Recordings obtained directly from the retina showed that FRO are highly dependent on halothane anesthesia levels. Notably, in a series of sessions we were able to record LGN responses in an awake cat, which was subsequently anesthetized by halothane, keeping the same recording site. FRO were completely absent in the awake condition and appeared strong as usual during the halothane anesthesia.

    Overall these results weaken substantially the notion that FRO are meaningful for vision. Nevertheless, as shown from our single cell analysis, retinal oscillations have many of the properties of cortical gamma oscillations. In this respect, oscillations in the retina induced by halothane serve as a valuable toolkit, even though artificial, for studying oscillatory neuronal dynamics.
7
  • ANA MARIA ARAÚJO SOARES
  • Implementações metodológicas para o estudo de comportamento social e emocional em um modelo animal de autismo

  • Leader : RODRIGO NEVES ROMCY PEREIRA
  • MEMBRES DE LA BANQUE :
  • RODRIGO NEVES ROMCY PEREIRA
  • MARCELO CAIRRÃO ARAUJO RODRIGUES
  • CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
  • Data: 30 oct. 2015


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  • O autismo é um transtorno do desenvolvimento que se manifesta nos primeiros anos de vida e apresenta semiologia heterogênea. Esta patologia afeta a maturação do encéfalo e produz alterações sensoriais, de linguagem e de interação social no início na infância. O modelo experimental de autismo utilizando ácido valproico (VPA) durante o período gestacional tem sido demonstrado ter alta validade de face e permitir estudos tanto das bases neuropatológicas quanto neuro-funcionais durante o desenvolvimento. A despeito do recente interesse por este modelo como instrumento de compreensão dos aspectos básicos da fisiopatologia do autismo, a maioria dos estudos experimentais têm se concentrado nos aspectos comportamentais, histológicos e celulares. Neste trabalho, foram propostas estratégias experimentais de avaliação comportamental associadas a eletrofisiologia \textit{in vivo}, uma técnica que nunca fora utilizada para avaliação desse modelo. Animais controles e experimentais, submetidos previamente a um procedimento cirúrgico para implante de eletrodos crônicos, participaram de experimentos de livre exploração, interação social e condicionamento ao medo.

     

Thèses
1
  • VITOR LOPES DOS SANTOS
  • CONTRIBUIÇÕES PARA O ESTUDO DO CÓDIGO NEURAL

  • Leader : SIDARTA TOLLENDAL GOMES RIBEIRO
  • MEMBRES DE LA BANQUE :
  • MADRAS VISWANATHAN GANDHI MOHAN
  • ADRIANO BRETANHA LOPES TORT
  • RICHARDSON NAVES LEAO
  • SIDARTA TOLLENDAL GOMES RIBEIRO
  • BRUSS REBOUÇAS COELHO LIMA
  • MÁRCIO FLÁVIO DUTRA MORAES
  • Data: 25 févr. 2015


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  •    Os recentes avanços técnicos das duas últimas décadas para o registro de sinais neuroeletrofisiológicos foram essenciais para que se testassem hipóteses há muito propostas acerca de como células nervosas processam e armazenam informação. No entanto, ao permitir maior detalhamento dos dados coletados, as novas tecnologias levam inevitavelmente ao aumento de sua complexidade estatística e, consequentemente, à necessidade de novas ferramentas matemático-computacionais para sua análise.

           Nesta tese, apresentamos novos métodos para a análise de dois componentes fundamentais nas atuais teorias da codificação neural: (1) assembleias celulares, definidas pela co-ativação de subgrupos neuronais; e (2) o padrão temporal de atividade de neurônios individuais. Em relação a (1), desenvolvemos um método baseado em análise de componentes independentes para identificar e rastrear padrões de co-ativação significativos com alta resolução temporal. Superamos limitações de métodos anteriores, ao efetivamente isolar assembleias e abrir a possibilidade de analisar simultaneamente grandes populações neuronais. Em relação a (2), apresentamos uma nova técnica para a extração de padrões de atividade em trens de disparo baseada na decomposição wavelet. Demonstramos, por meio de simulações e de aplicação a dados reais, que nossa ferramenta supera as mais utilizadas atualmente para decodificar respostas de neurônios e estimar a informação de Shannon entre trens de disparos e estímulos externos.
2
  • STÉFANO PUPE JOHANN
  • Ex Uno Plures: Sobre o uso de camundongos transgênicos e optogenética para caracterizar populações de neurônios identificadas geneticamente

     


  • Leader : RICHARDSON NAVES LEAO
  • MEMBRES DE LA BANQUE :
  • RICHARDSON NAVES LEAO
  • DIEGO ANDRES LAPLAGNE
  • VINICIUS ROSA COTA
  • MARTIN PABLO CAMMAROTA
  • OLAVO BOHRER AMARAL
  • Data: 20 mars 2015


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  • Os neurocientistas tem uma diversidade de perspectivas com as quais podem classificar diferentes partes do cérebro. Com o surgimento de técnicas baseadas na genética, como a optogenética, se torna cada vez mais importante identificar se um grupo de células, definidas através de morfologia, função ou posição anatômica possui um padrão característico de expressão de um ou mais promotores genéticos. Isso permitiria melhores formas de estudar essas populações de neurônios definidas geneticamente. Neste trabalho, eu apresento uma discussão teórica e três estudos experimentais nos quais essa foi a principal questão sendo abordada. O Estudo I discute as questões envolvidas em selecionar um promotor para estudar estruturas e subpopulações na Área Tegmental Ventral. O Estudo II caracteriza uma subpopulação de células na Área Tegmental Ventral que compartilha a expressão de um promotor, que é anatomicamente muito restrita, e que induz aversão quando estimulada. O Estudo II utiliza uma estratégia similar para investigar a subpopulação no núcleo subtalâmico que expressa PITX2 e VGLUT2 que, quando inativada, causa hiperlocomoção. O Estudo IV explora o fato de que um grupo de células previamente identificadas no Hipocampo Ventral expressa CHRNA2, e indica que essa subpopulação pode ser necessária e suficiente para o estabelecimento do ritmo teta (2-8 Hz) no Hipocampo Ventral de camundongos anestesiados. Todos esses estudos foram guiados pela mesma estratégia de identificar um promotor genético capaz de permitir o controle de uma população de neurônios identificada geneticamente, e eles demonstram as diferentes formas em que essa abordagem pode generar novas descobertas.

3
  • ARON DE MIRANDA HENRIQUES ALVES
  • REORGANIZAÇÃO DE REDES NEURAIS APÓS O ESTRESSE SOCIAL

  • Leader : CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
  • MEMBRES DE LA BANQUE :
  • DIEGO ANDRES LAPLAGNE
  • ISABEL MARIAN HARTMANN DE QUADROS
  • RICHARDSON NAVES LEAO
  • WILFREDO BLANCO FIGUEROLA
  • CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
  • Data: 16 déc. 2015


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  • Os objetivos da presente tese foram os de investigar padrões comportamentais e eletrofisiológicos associados à resiliência e suscetibilidade ao estresse social induzido em camundongos. Para isso, foi utilizado um protocolo de indução de estresse crônico contínuo a partir de derrotas sociais baseado no paradigma intruso-residente. Os resultados da tese são apresentados em dois estudos. No primeiro estudo, camundongos C57BL/6j submetidos a repetidos episódios de derrota social apresentaram motivação tardia para interagir com um camundongo desconhecido em sessões prolongadas (10 min) do teste de interação social. Utilizando uma abordagem etológica associada à análise computacional de vídeos foi possível rastrear precisamente a posição dos camundongos durante a realização de comportamentos de investigação social. Com isso, foi analisada a expressão detalhada de comportamentos defensivos, tais como investigação em postura estendida e fugas, associados ao comportamento de investigação social. A partir dessas análises, foi demonstrado que a realização do comportamento de investigação social em postura estendida foi significativamente maior para o grupo derrotado em comparação com o grupo controle. Ainda, um subgrupo de camundongos derrotados apresentou investigação social em postura estendida de forma persistente e sem habituação. Utilizando uma medida da distância de investigação durante as investigações sociais foi possível calcular um índice de aproximação (IA) para cada animal e separar um subgrupo apresentando fenótipo relacionado à ansiedade. A incidência de fugas também foi maior no grupo derrotado em comparação com os controles. A persistência na ocorrência desse comportamento foi observada em um subgrupo de camundongos submetidos às derrotas sociais. Calculamos então um índice de fugas (IF) que se correlacionou inversamente com a preferência por sacarose, sendo útil para identificar animais anedônicos. No segundo estudo, foram combinados análise etológica e registros eletrofisiológicos com tetrodos na área tegmentar ventral de camundongos submetidos à derrotas sociais. Utilizando critérios eletrofisiológicos e farmacológicos, foram classificadas as unidades registradas na área tegmentar ventral como supostos neurônios dopaminérgicos e não-dopaminérgicos. Foram analisadas a atividade desses neurônios durante o comportamento de investigação social e observado que a modulação da taxa de disparo dessas subpopulações neuronais distintas ocorreu de maneira oposta em animais suscetíveis e resilientes ao estresse social. Em suma, propomos que sessões prolongadas associadas à análise etológica detalhada durante os testes de interação social podem prover informação para classificação de camundongos em resilientes e susceptíveis após repetidas derrotas sociais. Ainda, a expressão do fenótipo suscetível parece estar associada ao comprometimento do sistema dopaminérgico mesolímbico na atribuição de valor de incentivo às interações sociais normalmente associadas ao aumento da atividade neuronal mesolímbica.

2014
Thèses
1
  • JULIANA MARTINS DE ASSIS
  • Codificação de Estímulos Sonoros por Potenciais Pós-Sinápticos e Potenciais de Campo Local

  • Leader : ADRIANO BRETANHA LOPES TORT
  • MEMBRES DE LA BANQUE :
  • ADRIANO BRETANHA LOPES TORT
  • KERSTIN ERIKA SCHMIDT
  • JEAN FABER FERREIRA DE ABREU
  • Data: 3 juil. 2014


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  • O processo de codificação é um aspecto fundamental do funcionamento cerebral. A transformação de estímulos sensoriais em respostas neurofisiológicas tem sido objeto de estudo em diversas áreas da Neurociência. Um dos modos mais utilizados para medir a eficiência de um código neural é pelo uso de medidas advindas da Teoria da Informação, como a informação mútua. Utilizando estas ferramentas, estudos recentes mostraram que no córtex auditivo tanto registros de potenciais de campo local (LFPs - local field potentials) quanto os tempos de disparos de potenciais de ação codificam informação sobre estímulos sonoros. Todavia, não há estudos aplicando ferramentas da Teoria da Informação para investigar a eficiência de códigos que utilizem potenciais pós-sinápticos (PSPs - postsynaptics potentials), isoladamente e em conjunto com análises de LFPs. Estes sinais estão relacionados visto que os LFPs são em parte construídos pela ação conjunta de vários PSPs. A presente dissertação reporta medidas de informação mútua entre respostas de PSPs e LFPs obtidas no córtex auditivo primário de ratos anestesiados e estímulos sonoros de frequências distintas. Nossos resultados mostram que respostas de PSPs possuem informação sobre estímulos sonoros, em níveis comparáveis e mesmo maiores que as respostas de LFPs. Também encontramos que PSPs e LFPs codificam informação sonora independentemente, uma vez que a análise conjunta destes sinais não mostrou sinergia nem redundância

2
  • DANIEL GOMES DE ALMEIDA FILHO
  • Uma investigação das sequências de fase Hebbianas descritas como grafos de assembleias neuronais

  • Leader : SIDARTA TOLLENDAL GOMES RIBEIRO
  • MEMBRES DE LA BANQUE :
  • DIEGO ANDRES LAPLAGNE
  • SERGIO TULIO NEUENSCHWANDER MACIEL
  • JEFFERSON ANTONIO GALVES
  • Data: 22 juil. 2014


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  • Hebb propôs que sinapses entre neurônios que disparam de forma síncrona são fortalecidas formando assembleias de células e sequências de fase. A primeira, numa escala menor, é um conjunto de células sincronizadas, que funcionam de forma transitória como um sistema fechado de processamento; a última, numa escala maior, corresponde à ativação sequencial de assembleias de células neuronais capazes de representar percepções e comportamentos. Atualmente, o registro de grandes populações neuronais permite a detecção simultânea de diversas assembleias neuronais. No âmbito da teoria de Hebb, o próximo passo lógico é a análise das sequências de fase. Neste trabalho investigamos seqüências de fase como padrões de ativações consecutivas de assembleias, analisando a relação entre comportamento animal e atributos de grafos de assembleias. Foram estudados trens de disparo neuronal registrados no hipocampo e neocórtex de 5 ratos adultos, antes, durante e depois da exploração de novos objetos (períodos experimentais). Para definir um grafo de assembleia, cada assembleia correspondeu a um nó, e cada aresta correspondeu à sequência temporal de ativação de nós consecutivos. A soma da ativação de todas as assembleias foi proporcional à taxa de disparo, mas a atividade de assembleias individuais não. O repertório de assembleias permaneceu estável ao longo dos períodos experimentais, indicando que a experiência com novos objetos não criou novas assembleias no rato adulto. Os atributos de grafos das assembleia, por outro lado, variaram significativamente entre os estados comportamentais e períodos experimentais e foram distintos o suficiente para permitir a classificação automática dos períodos experimentais (classificador Naive Bayes; AUROCs
    máximas variaram entre 0,55 a 0,99) e estados comportamentais (vigília, sono de ondas lentas e sono de movimento rápido dos olhos; AUROCs máximas variaram entre 0,64 e 0,98). Nossos achados reforçam a teoria Hebbiana de que as assembleias neuronais correspondem a estruturas primitivas de representação, quase inalteradas na maturidade, enquanto as seqüências de fase são instáveis entre os estados comportamentais e mudam após novas experiências. Os resultados são compatíveis com um papel das sequências de fase no comportamento e cognição.

3
  • GEISSY LAINNY DE LIMA ARAÚJO
  • Efeitos da sinalização por Sonic Hedgehog sobre a proliferação de células-tronco neurais e gliogênese no córtex cerebral em desenvolvimento

  • Leader : MARCOS ROMUALDO COSTA
  • MEMBRES DE LA BANQUE :
  • RODRIGO NEVES ROMCY PEREIRA
  • MARCOS ROMUALDO COSTA
  • CECILIA HEDIN PEREIRA
  • Data: 15 oct. 2014


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  • O Sonic Hedgehog (Shh) é um morfógeno com importantes ações no sistema nervoso central (SNC) em desenvolvimento, assim como na vida adulta em quadros de lesão tecidual e processos tumorigênicos. A relação da sua via de sinalização com proliferação, diferenciação e sobrevivência celular é amplamente estudada em regiões ventrais do SNC. No entanto, o papel da sinalização por Shh em egiões dorsais, como o telencéfalo dorsal, origem do córtex cerebral, não está bem documentada. A partir do cultivo de células de roedores retiradas do telencéfalo dorsal em desenvolvimento, observamos a influência do Shh sobre a proliferação e diferenciação das células-tronco neurais. Utilizando vídeo-microscopia de tempo intervalado, podemos avaliar o tempo de ciclo celular, tamanho de células progenitoras antes da divisão celular e tipo de divisão sofrida pelas células na presença ou na ausência de sinalização por Shh. Verificamos um aumento do número de células em estado proliferativo assim como um aumento de células reativas para o marcador astrocitário GFAP com o tratamento com Shh. Em contrapartida, após bloqueio da sinalização por Shh, observamos um menor número de células em estado proliferativo, desaceleração do ciclo celular, aumento da morte celular e redução da astrogliogênese. Por fim, com intuito de avaliar a influencia do Shh in vivo, nós injetamos fármacos agonista (Purmorfamina) e antagonista (Ciclopamina) da via de sinalização dessa proteína em diferentes períodos da gestação de roedores. Ao avaliar os animais na vida pós-natal, observamos um aumento no número de progenitores gliais gerados com o tratamento com Purmorfamina na substância branca, enquanto na substância cinzenta não parece haver alteração dessa população em ambos os tratamentos. Além disso, a população de células astrocitárias, evidenciada por marcadores específicos, parece estar alterada com a manipulação da sinalização por Shh. Em conjunto, nossos dados sugerem que a Shh está presente no telencéfalo dorsal em períodos precoces do desenvolvimento e influencia a geração, sobrevivência e proliferação de progenitores e células gliais.

4
  • ANNIE DA COSTA SOUZA
  • Estimulação optogenética do septo medial no rato anestesiado e em livre comportamento.

  • Leader : SIDARTA TOLLENDAL GOMES RIBEIRO
  • MEMBRES DE LA BANQUE :
  • VINICIUS ROSA COTA
  • EMELIE KATARINA SVAHN LEAO
  • RICHARDSON NAVES LEAO
  • SIDARTA TOLLENDAL GOMES RIBEIRO
  • CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
  • Data: 15 oct. 2014


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  • O ritmo teta consiste em uma oscilação eletrofisiológica hipocampal presente em várias espécies de mamíferos (4-12 Hz, com variações entre espécies). Essa oscilação está presente durante a vigília ativa de ratos e também é predominante no PCL desta espécie durante o sono de movimento rápido dos olhos (sono REM). Vários trabalhos demonstraram que o ritmo teta é importante em tarefas cognitivas. O septo medial é uma região importante na geração do ritmo teta hipocampal. Possui projeções colinérgicas, GABAérgicas e glutamatérgicas para o hipocampo, que por sua vez, possui projeções de feedback para o septo. Além do septo, outras regiões estão envolvidas na regulação do teta, formando uma rede complexa de interação e coordenação entre áreas que resultam no ritmo. A optogenética é uma ferramenta desenvolvida recentemente que tem sido amplamente utilizada em pesquisas de diversas áreas. Ela nos permite manipular a atividade elétrica de neurônios através de estimulação luminosa. A técnica consiste em, através de um vetor viral, induzir a expressão neuronal de canais iônicos associados a opsinas (ex.: ChR2), que uma vez infectados passam a ser sensíveis a luz de determinado comprimento de onda. O presente trabalho de pesquisa de mestrado teve como objetivo implantar a optogenética em animais em livre comportamento pioneiramente no Brasil, através de experimentos com implantes crônicos de eletrodos e fibras óptica em animais infectados com vetor viral para expressão de ChR2. Foram realizadas cirurgias de injeções de vírus no septo medial; resultados histológicos confirmaram a expressão de ChR2 através da marcação da
    proteína repórter eYFP no septo e também em processos hipocampais. Além disso, foram realizados experimentos agudos com estimulação luminosa do septo medial e registro de potenciais de campo local (PCL) no próprio septo e hipocampo em animais anestesiados. Ainda nesses experimentos foi possível registrar potenciais de ação no septo. Nesses experimentos observamos aumento da taxa de disparo dos neurônios septais durante estimulação luminosa (n=300 estímulos). Além disso, encontramos uma resposta evocada no PCL do hipocampo no início do pulso luminoso. Também foram realizados experimentos crônicos com estimulação luminosa do septo medial e registro de PCL do hipocampo em animais em livre comportamento. Através de análise do PCL, verificamos se a estimulação luminosa do septo é capaz de induzir ritmo teta no hipocampo.

Thèses
1
  • FABIO VIEGAS CAIXETA
  • EFEITOS DA ADMINISTRAÇÃO AGUDA DE QUETAMINA SOBRE AS OSCILAÇÕES ELETROFISIOLÓGICAS DA REGIÃO CA1 HIPOCAMPAL

  • Leader : ADRIANO BRETANHA LOPES TORT
  • MEMBRES DE LA BANQUE :
  • RICHARDSON NAVES LEAO
  • SERGIO TULIO NEUENSCHWANDER MACIEL
  • ADRIANO BRETANHA LOPES TORT
  • MARIA ELISA CALGANOTTO
  • OLAVO BOHRER AMARAL
  • Data: 5 févr. 2014


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  • Em humanos, a administração de quetamina - um antagonista não-competitivo do receptor glutamatérgico do tipo NMDA - causa um amplo espectro de sintomas associados à esquizofrenia. Dado o papel dos ritmos cerebrais na realização de tarefas cognitivas, tem sido sugerido que a patofisiologia da esquizofrenia estaria relacionada a desordens de oscilações corticais. Neste estudo utilizamos o registro do potencial de campo elétrico em múltiplos eletrodos implantados no hipocampo de ratos sob o efeito de injeções sistêmicas de doses sub-anestésicas de quetamina (25, 50 e 75 mg/kg IP) para investigarmos as alterações comportamentais e eletrofisiológicas neste modelo animal de psicose. A quetamina alterou o padrão de locomoção e causou diversas mudanças na dinâmica de oscilações neurais. A potência nas bandas de frequência gama e oscilações de alta frequência (OAF) aumentou em todas as profundidades do eixo CA1-giro denteado, enquanto a potência de teta variou dependendo da camada registrada. A coerência de fase de gama e de OAF aumentou entre as camadas de CA1. A quetamina aumentou o acoplamento entre frequências (AEF) de fase-amplitude entre teta e OAF em todas as doses, mas teve efeitos opostos no AEF entre teta e gama de acordo com a dose. Nossos resultados demonstram que o modelo de esquizofrenia induzido por hipofunção dos receptores NMDA está associado com alterações de interações de alta ordem entre oscilações neurais.

2
  • SERGIO ANDRÉS CONDE OCAZIONEZ
  • The influence of visual inter-hemispheric connections on spiking, assembly and LFP activities, and their phase relationship during figure-ground stimulation.

  • Leader : KERSTIN ERIKA SCHMIDT
  • MEMBRES DE LA BANQUE :
  • JEAN CHRISTOPHE HOUZEL
  • KERSTIN ERIKA SCHMIDT
  • ADRIANO BRETANHA LOPES TORT
  • SERGIO TULIO NEUENSCHWANDER MACIEL
  • JEROME PAUL ARMAND LAURENT BARON
  • Data: 31 mars 2014


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  • Since Hubel and Wiesel’s pioneer finding a vast body of literature has accumulated describing neuronal responses in the primary visual cortex (V1) to different visual stimuli. These stimuli mainly consisted of moving bars, dots or gratings which served to explore the responses to basic visual features such as orientation, direction of motion or contrast, among others, within a classical receptive field (CRF). However, in the last two decades it became increasingly evident that the activity of V1 neurons can be modulated by stimulation outside their CRF. Thus, early visual areas might be already involved in more complex visual tasks like, for example, the segmentation of an object or a figure from its (back)-ground. It is assumed that intrinsic long-range horizontal connections within V1 as well as feedback connections from higher visual areas are actively involved in the figure-ground segmentation process. Their possible role has been inferred from the analysis of the spike rate variations induced by stimuli placed outside the CRF of single neurons. Although it is very likely that those connections also have an impact on the joined activity of neurons involved in processing the figure and on their local field potentials (LFP), these issues remain understudied.

    In order to examine the context-dependent modulation of those activities, we recorded spikes and LFPs in parallel from up to 48 electrodes in the primary visual cortex of anesthetized cats. We stimulated with composite grating and natural scene stimuli focusing on populations of neurons whose CRFs were situated on the foreground figure. In addition, in order to examine the influence of horizontal connections we removed the inter-hemispheric input of the isotopic contralateral visual areas by means of reversible cooling deactivation.

    We did so because i) the intrinsic horizontal connections cannot be easily manipulated without directly affecting the measured signals, ii) because inter-hemispheric connections share the major anatomical features with the intrinsic lateral network and can be seen as a functional continuation of the latter across the two hemispheres and iii) because cooling causally and reversibly deactivates input connections by temporarily silencing the sending neurons and thus enables direct conclusions on their contribution.

    Our results demonstrate that the figure-ground segmentation mechanism is reflected in the spike rate of single neurons, as well as in their LFP power and its phase-relationship to the spike patterns produced by the population. In addition "lateral" inter-hemispheric connections modulate spike rates and LFP power depending on the stimulation of the neurons’ CRF surround. Further, we observe an influence of this lateral circuit on field-
    field coherences between remote recording sites. In conclusion, our findings support the idea of complex figure-ground segmentation mechanism acting already in early visual areas on different time scales. This mechanism seems to involve groups of neurons firing synchronously and dependent on the LFP’s phase. Our results are also compatible with the hypothesis that long-range lateral connections contribute to that mechanism.

3
  • ANDREA LIMA DE SA
  • PLASTICIDADE DEPENDENTE DA EXPERIENCIA INDUZIDA POR MANIPULAÇÃO DA MATRIZ EXTRACELULAR

  • Leader : ANTONIO PEREIRA JUNIOR
  • MEMBRES DE LA BANQUE :
  • CARLOMAGNO PACHECO BAHIA
  • WALACE GOMES LEAL
  • LIA REJANE MULLER BEVILAQUA
  • ANTONIO PEREIRA JUNIOR
  • JOHN FONTENELE ARAUJO
  • Data: 5 sept. 2014


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  • O córtex somatosensorial primário (S1), recebe informações dos receptores táteis localizados na periferia sensorial e desempenha um papel crucial na exploração ambiental. No entanto, essa região do SNC adulto, como várias outras, apresenta uma redução expressiva no seu potencial plástico na fase adulta. Esse fato se deve à presença de estruturas e substâncias que impedem a regeneração dos neuritos após a lesão, como por exemplo os componentes da matriz extracelular (MEC) presentes nas redes perineuronais. O amadurecimento das redes perineuronais (RPNs) coincide com o fechamento do período crítico de plasticidade, pois os proteoglicanos da matriz extracelular atuam na estabilização dos contatos sinápticos. A remoção dos componentes desta matriz é uma manobra promissora para o restabelecimento da plasticidade e da recuperação funcional de áreas lesionadas do sistema nervoso central de animais adultos. Na presente tese, realizamos a remoção das PGSCs do meio extracelular do córtex cerebral como terapia para restaurar a plasticidade e promover a regeneração morfofuncional do córtex somestésico primária (SI) após remoção das vibrissas mistaciais durante o período crítico. O tratamento com CABC mostrou-se eficaz para o estabelecimento de plasticidade cerebral com alterações axonais, celulares e recuperação funcional.

2013
Thèses
1
  • HERMANY MUNGUBA VIEIRA
  • Indicadores de cálcio e de voltagem codificados geneticamente na detecҫão de potenciais de aҫão e inputs sinápticos em cultura de neurônios hipocampais

  • Leader : RICHARDSON NAVES LEAO
  • MEMBRES DE LA BANQUE :
  • EMELIE KATARINA SVAHN LEAO
  • RICHARDSON NAVES LEAO
  • OLAVO BOHRER AMARAL
  • Data: 4 mars 2013


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  • Por décadas o imageamento óptico se mostrou uma técnica muito poderosa no estudo da atividade de neurônios, tanto in vitro como no cérebro intacto. Recentemente, indicadores ópticos codificados geneticamente surgiram como ferramentas de alta resolução espacial e temporal não-invasivos, utilizados para o monitoramento da atividade de neurônios individuais e de populações neuronais específicas. Tais indicadores optogenéticos são basicamente compostos por duas proteínas. A primeira atua como um biosensor que detecta alteraҫões referentes a um sinal fisiológico específico (como por exemplo concentraҫão de Ca2+, voltagem ou pH), sendo portanto o segmento que determina a sensibilidade da proteína-repórter. A segunda porҫão dos indicadores é por sua vez uma proteína fluorescente, que converte os sinais fisiológicos detectados em variações na emissão de fluorescência.O rápido aumento do número de novos indicadores optogenéticos, juntamente com a ausência de comparações desses indicadores sob condições idênticas gerou a dificuldade de escolher a proteína mais adequada, a depender do desenho experimental em questão. A proposta do nosso estudo foi comparar três proteínas-repórter recentemente desenvolvidas: os indicadores de cálcio GCaMP3 e R-GECO1 e o indicador de voltagem VSFP butterfly1.2. 
     
    Eles foram expressos em neurônios hipocampais em cultura, os quais foram submetidos às técnicas de patch-clamp e imageamento óptico. Após experimentos, algumas culturas foram fixadas e marcadas para sinapsina-1 e MAP2, demonstrando maturidade neuronal. Os três grupos (cada um expressando uma das proteínas) exibiram valores de potencial de membrana semelhantes (in mV GCaMP3: -56 ±8.0; R-GECO1: -57 ±2.5; VSFP: -60 ±3.9; p = 0,86); todavia, o grupo de neurônios expressando VSFP apresentou valor médio de resistência de input inferior aos demais grupos (in Mohms, GCaMP3: 161 ±18.3; R-GECO1: 128 ±15.3; VSFP: 94 ±14.0; p = 0,02). Cada neurônio foi submetido a protocolos de injeҫão de correntes em diferentes frequências (10 Hz, 5 Hz, 3 Hz, 1,5 Hz e 0,7 Hz) e registramos seu efeito sobre a emissão de fluorescência no tempo. Em nosso estudo, apenas 26,7% (4/15) dos neurônios expressando VSFP apresentaram sinal de fluorescência detectável em resposta a potenciais de aҫão. O valor médio da relaҫão sinal-ruído (SNR) obtido em resposta a cinco disparos (10 Hz) foi pequeno (1.3 ±0,21), porém a cinética rápida daVSFP permitiu a discriminaҫão de potenciais de aҫão como picos individuais, permitindo a detecҫão de 53% dos disparos evocados. Frequências inferiores a 5 Hz e sinais subliminares foram indetectáveis devido ao alto ruído. Por sua vez, os indicadores de cálcio mostraram a maior mudança na fluorescência após o mesmo protocolo (cinco disparos a 10 Hz). Dos neurônios expressando GCaMP3, 80% (8/10) exibiram sinal, com valor médio de SNR 21 ±6,69 (soma), enquanto para R-GECO1, 50% (2/4) dos neurônios possuíam sinal, com valor médio de SNR 52 ±19,7 (soma). Para a frequência de 10 Hz, foram detectados 54% dos disparos com GCaMP3 e 85% com R-GECO1. Potenciais de aҫão foram detectáveis nas frequências analisadas and foi detectado sinal de fluorescência também de despolarizaҫões subliminares.
     
    Pelo fato de GCaMP3 apresentar maior probabilidade de obtenҫão de sinal, bem como alto SNR, alguns experimentos foram realizados somente com essa proteína. Demonstramos que GCaMP3 é eficaz na detecҫão da entrada de inputs sinápticos (envolvendo influxo de Ca2+), com alta resoluҫão espacial e temporal. Observamos também diferenҫas entre o sinal decorrente de disparos evocados e de disparos ocorrendo espontaneamente. Nos registros em grupos celulares, GCaMP3 mostrou clara discriminaҫão entre células ativadas e em silêncio, bem como se revela uma ferramenta em potencial nos estudos de sicronizaҫão neuronal. Assim, nossos resultados indicam que os indicadores de cálcio atuais já permitem a execuҫão de estudos minuciosos de comunicaҫão neuronal, incluindo desde espinas dendríticas individuais até a alternativa de investigar eventos de sincronia em redes neuronais geneticamente definidas. Em contrapartida, embora ainda em aprimoramento, estudos com VSFPs representam uma tecnologia promissora para o monitoramento de atividade neural e poderá ser futuramente mais adequado do que os indicadores de cálcio, uma vez que neurônios trabalham em  uma escala de tempo mais veloz do que eventos de cálcio podem prever.
2
  • NATALIA BEZERRA MOTA
  • Análise de grafos aplicada a relatos de sonhos: ferramenta diagnóstica objetiva e diferencial para psicose esquizofrênica e bipolar.

  • MEMBRES DE LA BANQUE :
  • LEANDRO FERNANDES MALLOY-DINIZ
  • SANDRO JOSE DE SOUZA
  • MAURO COPELLI
  • Data: 26 juil. 2013


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  • Sendo o diagnóstico em psiquiatria essencialmente uma descrição subjetiva de sintomas, métodos quantitativos para uma classificação objetiva das desordens mentais são necessários. Distúrbios do pensamento caracterizados a partir da fala, assim como transtornos de linguagem em si, por séculos vêm sendo descritos como características marcantes de quadros psicóticos, produzindo sintomas como incoerência do discurso, empobrecimento da fala, afrouxamento de associações, muito comuns na esquizofrenia. Vendo a relação entre as palavras em um discurso como um sistema complexo, a partir da representação de relatos como grafos de co-ocorrência de palavras, pretendemos caracterizar sintomas observáveis na fala de psicóticos portadores de esquizofrenia ou transtorno bipolar do humor, contribuindo para diagnóstico objetivo e diferencial dessas desordens mentais. Para isso colhemos relatos de sonhos e de atividades realizadas durante a vigília de 60 sujeitos, (20 pacientes psicóticos portadores de esquizofrenia (E), 20 pacientes psicóticos portadores de transtorno bipolar do humor(B) (diagnóstico realizado com aplicação de SCID DSM-IV) e 20 sujeitos não psicóticos (C)), medindo sintomatologia psiquiátrica a partir de escalas psicométricas (PANSS e BPRS). Representando os relatos do sonho e da vigília por grafos onde cada palavra era equivalente a um nó e sua sequência no discurso era representada por arestas, foi possível caracterizar essas redes, extraindo 14 atributos de grafo. Mesmo após controlar diferenças do total de palavras em cada discurso, encontramos que E falavam com menor conectividade entre palavras que demais grupos, característica correlacionada negativamente com sintomas negativos e cognitivos medidos pelas escalas psicométricas. Quando falavam sobre vigília, B eram indistinguíveis dos C, mas falavam sobre sonhos com menos conectividade entre palavras que o último, usando menor diversidade de palavras. As medidas de grafo dessas redes permitiram diagnóstico objetivo (em relação ao C) de E (AUC: 0.931, mais de 90% sensibilidade e especificidade) com semelhante acurácia em relação à quantificação dos sintomas, além de objetivamente classificar B (AUC 0.745, mais de 70% de sensibilidade e especificidade), melhorando diagnóstico diferencial entre E e B (AUC 0.81, mais de 65% sensibilidade e especificidade), o qual não foi possível pela quantificação dos sintomas (AUC 0.376, menos de 40% de sensibilidade e especificidade). Utilizando medidas de grafos associadas à quantificação dos sintomas, simulando situação clínica com uso de redes de co-ocorrência de palavras como diagnóstico complementar, foi possível atingir níveis ótimos de acurácia para diagnóstico de E (AUC 1, 100% sensibilidade e especificidade), de B (AUC 0.928, mais de 80% de sensibilidade e especificidade), com boa classificação diferencial entre E e B (AUC 0.804, mais de 70% sensibilidade e especificidade). Os resultados mostram a ferramenta desenvolvida nesse mestrado como método promissor e acurado para diferenciar psicose esquizofrênica de psicose bipolar, além de constituir método automático e totalmente objetivo de diagnóstico dessas desordens. É possível ainda quantificar sintomas psiquiátricos atualmente com difícil caracterização subjetiva (como sintomas negativos e cognitivos, desordens do pensamento e da linguagem), abrindo possibilidades de uso para busca de biomarcadores. Adicionalmente revela-se que, quanto mais introspectivo o relato, maior a influência da psicopatologia na linguagem. A noção freudiana de que os sonhos são o caminho real para o inconsciente pode ser útil ao final.

3
  • JULIANA ALVES BRANDAO MEDEIROS DE SOUSA
  • Caracterização comportamental e distribuição de neurônios inibitórios em um modelo animal de autismo induzido por ácido valpróico

  • Leader : RODRIGO NEVES ROMCY PEREIRA
  • MEMBRES DE LA BANQUE :
  • MARCOS ROMUALDO COSTA
  • RODRIGO NEVES ROMCY PEREIRA
  • CARMEM GOTTFRIED
  • Data: 23 août 2013


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  • O autismo compreende um grupo heterogêneo de transtornos do desenvolvimento que afeta a maturação do encéfalo e produz alterações sensoriais, motoras, de linguagem e de interação social, de início na infância. Vários estudos indicam um importante envolvimento de fatores genéticos que levam à uma predisposição ao autismo, além de fatores ambientais que podem influenciar a vida embrionária e pós-natal. Estudos recentes, em modelos animais, indicam que alterações no controle epigenético durante o desenvolvimento possam gerar distúrbios de maturação neuronal e produzir circuitarias hiper-excitáveis, resultando em sintomas típicos do autismo. No modelo animal de autismo induzido por administração de ácido valpróico (VPA) durante a gestação de ratas, foram observadas alterações comportamentais, eletrofisiológicas e celulares semelhantes às observadas nos pacientes autistas. Entretanto, ainda são poucos os estudos que correlacionam as alterações comportamentais com a suposta hiper-excitabilidade neuronal desse modelo. Portanto, o objetivo deste trabalho foi inicialmente gerar o modelo animal de autismo por exposição pré-natal a ácido valpróico, e então avaliar o desenvolvimento e comportamento pós-natal em animais pré-púberes (P30). Além disso, pretendemos quantificar e analisar a distribuição de neurônios inibitórios no córtex pré-frontal e cerebelo dos animais VPA comparando-os com animais controle. Para isso, acompanhamos o desenvolvimento desses animais e realizamos testes de atividade exploratória e locomotora, auto-limpeza, reconhecimento de objetos e interação social. Quantificamos interneurônios imunorreativos para parvalbumina no córtex pré-frontal medial (CPFm) e células de Purkinje do cerebelo para avaliar a ocorrência de alterações celulares envolvidas em hiper-excitabilidade cortical. Nossos resultados mostram que o tratamento com VPA foi capaz de induzir alterações no desenvolvimento dos animais, refletindo-se em alterações comportamentais como hiperlocomoção, comportamento repetitivo e déficit de interação social. A quantificação celular revelou uma diminuição no número de interneurônios parvalbuminérgicos no córtex cingulado anterior e na região pré-límbica do CPFm, sugerindo um desbalanço excitatório-inibitório neste modelo de autismo. Observamos também que a redução neuronal ocorreu preferencialmente nas camadas II/III e V/VI do córtex. Esperamos que nossos resultados possam contribuir para o maior entendimento das alterações celulares neste modelo de autismo, assim como esclarecer suas implicações funcionais.

4
  • FÁBIO BATISTA FREITAG

  • ENCODING MECHANISMS BASED ON FAST OSCILLATIONS IN THE RETINA OF THE CAT AND THEIR DEPENDENCIES ON ANESTHESIA

  • Leader : SERGIO TULIO NEUENSCHWANDER MACIEL
  • MEMBRES DE LA BANQUE :
  • JEROME PAUL ARMAND LAURENT BARON
  • SERGIO TULIO NEUENSCHWANDER MACIEL
  • ADRIANO BRETANHA LOPES TORT
  • Data: 27 août 2013


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  • Processing in the visual system starts in the retina. Its complex network of cells with different properties enables for parallel encoding and transmission of visual information to the lateral geniculate nucleus (LGN), where information is subsequently processed and transmitted to the cortex. In the retina, it has been shown that responses are often accompanied by fast synchronous oscillations (30 - 90 Hz) in a stimulus-dependent manner. Studies in the frog, cat and monkey, have found that retinal oscillations are very strong for responses to large stimuli and that they probably encode global stimulus properties, such as size and continuity (Neuenschwander and Singer, 1996; Ishikane et al., 2005). Moreover, simultaneous recordings from different levels in the visual system have shown that the oscillatory patterning of retinal ganglion cell responses are transmitted to the cortex via the LGN (Castelo-Branco et al., 1998). Overall these results suggest that feedforward synchronous oscillations contribute to visual encoding. In the present study on the LGN of the anesthetized cat, we further investigate the role of retina oscillations in early visual processing by applying complex stimuli, such as natural visual scenes, light spots of varying size and contrast, and flickering checkerboards. This is a necessary step for understanding encoding mechanisms in more naturalistic conditions, since most data on retinal oscillations have been obtained for responses to simple, flashed and stationary stimuli. Correlation analysis of spiking responses confirmed previous results showing that oscillatory responses in the retina (observed here from the LGN responses) largely depend on the size and stationarity of the stimulus. For natural scenes (full gray-level and binary movies) oscillations appeared only for brief moments when receptive fields were dominated by large continuous, flat-contrast surfaces. Oscillatory activity seemed to be dependent on a critical mass of activated cells suggesting that it arises from large-scale horizontal interactions in the retina. Moreover, our results show that retinal oscillations in the cat are surprisingly dependent on the halothane anesthesia. In the absence of halothane, oscillatory activity vanished independent of the characteristics of the visual stimulus. The same findings were obtained for isoflurane, which has similar pharmacological properties. These new and unexpected results question whether feedfoward oscillations in the early visual system are simply due to an imbalance between excitation and inhibition in the retinal networks generated by the halogenated anesthetics. Further studies in awake behaving animals are necessary to extend these conclusions.

5
  • ANDERSON BRITO DA SILVA
  • Revisitando a eletrocorticografia intra-operatória: Relevância das oscilações de alta frequência

  • Leader : CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
  • MEMBRES DE LA BANQUE :
  • ADRIANO BRETANHA LOPES TORT
  • CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
  • LUCIANA PATRIZIA ALVES DE ANDRADE VALENÇA
  • Data: 13 déc. 2013


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  • As epilepsias são desordens neurológicas caracterizadas por crises espontâneas e recorrentes resultado de uma atividade elétrica anormal de uma determinada rede neural. Dentre os diferentes tipos de epilepsia, a epilepsia mesial do lobo temporal (EMLT) é a mais comumente observada em seres humanos, sendo frequentemente associada a esclerose hipocampal. Infelizmente, nem todos os pacientes se beneficiam do tratamento farmacológico (pacientes fármaco-resistentes) e tornam-se, portanto, candidatos ao tratamento cirúrgico, um procedimento de alta complexidade e elevado custo. Hoje, a lobectomia temporal anterior com amigdalo-hipocampectomia seletiva é a cirurgia de epilepsia mais frequentemente realizada. Entretanto, uma parcela significativa de pacientes continua a apresentar crises debilitantes mesmo após o tratamento cirúrgico. Assim, compreender o encéfalo epiléptico humano é fundamental no refinamento do tratamento cirúrgico com o objetivo de aumentar a eficiência desse procedimento terapêutico.

    O objetivo da presente dissertação foi identificar e quantificar a ocorrência de atividade epileptiforme (espículas interictais, EI e oscilações de alta frequência, OAF) em registros eletrocorticográficos (ECoG) realizados durante procedimento cirúrgico em pacientes com epilepsia mesial do lobo temporal refratária ao tratamento farmacológico (protocolo aprovado pelo CEP / Unifesp; #1038/03). 

    Registros ECoG (Nihon-Koden, 32 canais @ 1kHz) foram realizados na superfície do lobo temporal e no giro para-hipocampal em 3 momentos cirúrgicos: no córtex intacto, após lobectomia temporal anterior e após amigdalo-hipocampectomia (duração média de cada um desses registros: 10 min; N=17 pacientes). A ocorrência de EI e OAF foi quantificada automaticamente, por meio de rotinas em Matlab, e validadas visualmente. Frequência dos eventos (número de eventos/canal) em cada um dos tempos cirúrgicos foram correlacionadas com resultado cirúrgico quanto ao controle das crises. 

    De um total de 8 h e 40 min de registro, 36.858 EI e 2.326 EAF foram identificadas. Os pacientes com melhor prognóstico cirúrgico apresentaram maior quantidade de OAF antes da cirurgia, porém não diferiram quanto a frequência, morfologia e distribuição de EI. A ocorrência de OAF no registro basal apresentou melhor desempenho que as EI na previsão do controle total das crises no pós operatório (EI: AUC = 57%, S = 70% , E = 71% vs OAF: AUC = 77%, S = 70%, E=100%). O mesmo foi observado com o parâmetro a variação da área irritativa entre os momentos pré- e pós-ressecção (EI: AUC = 54%, S = 60%, E = 71% vs OAF: AUC = 84%, S = 80%, E = 100%). Nesse caso, o classificador foi capaz de identificar todos os pacientes de pior prognóstico, apresentando apenas dois falsos positivos. 

    O presente trabalho demonstra que as OAF podem ser encontradas no registro ECoG intra-operatório, na presença de anestésicos, em uma curta sessão de registro, juntamente com as EI. A observação de que a ocorrência desses eventos no início da cirurgia permite classificar o paciente quanto ao prognóstico cirúrgico é surpreendente e abre caminho para aplicar o ECoG intra-operatório, por exemplo, na decisão sobre o uso de tratamento farmacológico adjuvante ou da conversão para ressecções individualizadas. O mecanismo responsável por esse efeito ainda é desconhecido.

2012
Thèses
1
  • PRISCILA TAVARES MACÊDO
  • A CAFEÍNA EXERCE EFEITOS POSITIVOS SOBRE A MEMÓRIA TIPO-EPISÓDICA EM RATOS ADULTOS SEM INFLUENCIAR A SOBREVIVÊNCIA NEURONAL NO GIRO DENTEADO

     

  • Leader : REGINA HELENA DA SILVA
  • MEMBRES DE LA BANQUE :
  • REGINA HELENA DA SILVA
  • VANESSA COSTHEK ABILIO
  • RODRIGO NEVES ROMCY PEREIRA
  • Data: 27 avr. 2012


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  • A cafeína é um leve psicoestimulante que em baixas doses tem efeitos cognitivos e mnemônicos positivos, enquanto em altas doses tende a possuir efeitos prejudiciais sobre esses processos. A memória tipo-episódica em roedores pode ser avaliada com tarefas hipocampo-dependentes. O giro denteado é uma subregião hipocampal onde ocorre neurogênese no adulto, e acredita-se que esse processo esteja relacionado à sua função de separação de padrões, ou seja, identificação de padrões espaço-temporais para discriminar eventos. Além disso, a neurogênese é influenciada pelo aprendizado de tarefas espaciais e contextuais. Nosso objetivo foi avaliar os efeitos comportamentais em tarefas tipo-episódicas, em ratos Wistar machos, submetidos a tratamentos agudo ou crônico com cafeína, nas doses de 15mg/kg ou 30mg/kg. Além disso, procuramos avaliar as relações do efeito crônico da cafeína, em doses baixa e elevada, bem como da influência do aprendizado de tarefas hipocampo-dependentes, sobre a sobrevivência de neurônios nascidos no início do tratamento, fazendo uso de BrdU para marcar novas células geradas no giro denteado. Quanto ao tratamento agudo, vimos que o grupo salina tendeu a apresentar melhor discriminação temporal e espacial que os grupos cafeína, nas tarefas executadas. Os resultados do tratamento crônico mostraram que houve melhor discriminação do grupo cafeína 15 mg/kg (dose baixa) quanto ao aspecto temporal da memória episódica; já o grupo cafeína 30mg/kg (dose alta) conseguiu discriminar melhor temporalmente em condição de maior dificuldade de execução em comparação a menor dificuldade. Avaliação da neurogênese por meio de imunohistoquímica para contagem de novos neurônios gerados no giro denteado não revelou nenhuma diferença entre os grupos do tratamento crônico. Assim, os efeitos positivos mnemônicos do tratamento crônico com cafeína não estão relacionados com a sobrevivência neuronal. Entretanto, outro mecanismo plástico deve explicar o efeito mnemônico positivo, haja vista que não houve melhora nos grupos tratados com cafeína administrada agudamente.


     

     

2
  • FERNANDA PALHANO XAVIER DE FONTES
  • Alterações da default mode network provocadas pela ingestão de Ayahuasca investigadas por Ressonância Magnética Funcional

  • Leader : DRAULIO BARROS DE ARAUJO
  • MEMBRES DE LA BANQUE :
  • SIDARTA TOLLENDAL GOMES RIBEIRO
  • DRAULIO BARROS DE ARAUJO
  • EDSON AMARO JUNIOR
  • Data: 25 mai 2012


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  • A Ayahusca é uma bebida psicotrópica que tem sido utilizada há séculos por populações originais da América do Sul, notadamente da região Amazônica, com fins religiosos e medicinais. O chá é obtido pela decocção de folhas de Psychotria viridis com a casca e tronco de um arbusto, Banisteriopsis caapi. A primeira é rica em N,N-dimetiltriptamina (DMT), que tem importante e bem conhecido efeito alucinógeno devido a sua atuação agonista nos receptores de serotonina, especificamente 5-HT2A. Por outro lado, as b-carbolinas presentes na B. caapi, particularmente a harmina e a harmalina, são potentes inibidores da monoamina oxidase (iMAO). Além disso, a tetrahidroharmina (THH), também presente na B. caapi, atua como leve inibidor seletivo da recaptação de serotonina e um fraco inibidor de MAO. A DMT, por si só não é ativa por via oral, uma vez que é degradada pela MAO. No entanto, a presença de iMAO na bebida permite que a DMT seja psicoativa quando ingerida. O acesso da DMT à circulação sistêmica e ao sistema nervoso central provoca uma série de alterações afetivas, perceptivas e cognitivas. Além disso, os seus efeitos têm sido associados ao aumento da atenção interoceptiva. Por outro lado, existe um interesse crescente na rede de modo padrão (DMN), que tem sido amplamente detectada em estudos de neuroimagem funcional e tem sido associada com atividade mental introspectiva. Assim, este estudo teve como objetivo avaliar, por meio de ressonância magnética funcional – fMRI, as possíveis mudanças da DMN causadas pela ingestão da Ayahuasca em 10 voluntários saudáveis enquanto executavam uma tarefa de fluência verbal e protocolo de resting state. De maneira geral, observa-se que a Ayahuasca provoca redução na amplitude do sinal BOLD nos nodos centrais da DMN, tais como o cíngulo anterior, o córtex pré-frontal medial, o cíngulo posterior, o pré-cuneus e o lobo parietal inferior. Além disso, também foram observadas alterações no padrão de conectividade funcional da DMN, em particular, diminuição na conectividade funcional no pré-cuneus. Juntos, esses achados indicam que, sob efeito da Ayahuasca, os indivíduos apresentam um estado alterado de consciência, no qual o fluxo de pensamentos espontâneos é alterado, e sugerem um potencial uso terapêutico da Ayahuasca em transtornos mentais nos quais a DMN se mostra alterada.

3
  • BRUNA SOARES LANDEIRA
  • EFEITOS DA ELIMINAÇÃO DE NEURÔNIOS INFRAGRANULARES SOBRE A ESPECIFICAÇÃO DE NEURÔNIOS GRANULARES E SUPRAGRANULARES DO CÓRTEX CEREBRAL.

  • Leader : MARCOS ROMUALDO COSTA
  • MEMBRES DE LA BANQUE :
  • MARCOS ROMUALDO COSTA
  • CECILIA HEDIN PEREIRA
  • CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
  • Data: 10 août 2012


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  • O córtex cerebral de mamíferos encontra-se histologicamente organizado em camadas de neurônios excitatórios que, por sua vez, apresentam distintos padrões de conectividade com alvos corticais ou sub-corticais. Durante o desenvolvimento, estas camadas corticais são estabelecidas através de uma intricada combinação entre especificação neuronal e migração radial num padrão conhecido como "inside-out" (de dentro para fora). Desta forma, por exemplo, neurônios infragranulares nas camadas V e VI são gerados anteriormente aos neurônios granulares da camada IV, que por sua vez são gerados antes dos supra-granulares das camadas II e III. Na última década, foram identificados diversos genes codificando fatores de transcrição envolvidos na especificação sequencial de neurônios destinados às diferentes camadas corticais. No entanto, ainda pouco é sabido sobre a influência dos neurônios gerados previamente sobre a especificação das coortes neuronais subsequentes. Para investigar esta possibilidade, nós utilizamos um método de recombinação gênica  (sistema Cre-Lox) para induzir a morte seletiva de neurônios das camadas corticais V e VI antes da geração dos neurônios das camadas II, III e IV.  Dessa forma, podemos avaliar os efeitos da ablação de neurônios infragranulares sobre o fenótipo dos neurônios gerados em seguida. Nossos dados mostram que, um dia após a ablação, neurônios da camada VI expressando o fator de transcrição TBR1 voltaram a ser gerados enquanto praticamente nenhum neurônio expressando TBR1 foi gerado na mesma idade em animais controle.  Esse dado sugere que os progenitores envolvidos na geração de neurônios destinados às camadas superficiais sofrem interferência da morte seletiva de neurônios de camadas profundas, mudando sua especificação. Uma parte dos neurônios TBR1 se estabeleceu na camada VI e outra migrou até as camadas II e III, indicando que o controle dos padrões migratórios pode ser independente dos fenótipos neuronais.  Além disso, observamos que na população neuronal total também ocorreu um aumento na quantidade de neurônios de camada V expressando CTIP2 e uma alteração na distribuição dessas células. O mesmo foi observado para neurônios supragranulares expressando SATB2. Em conjunto, nossos dados indicam a existência de um mecanismo de controle exercido pelos neurônios gerados inicialmente no córtex cerebral sobre o destino dos progenitores envolvidos na geração dos demais neurônios corticais. Tal mecanismo poderia contribuir para o controle do número de neurônios em diferentes camadas e contribuir para o estabelecimento de diferentes áreas corticais. 

4
  • MORGANA MENEZES NOVAES
  • Avaliação por Ressonância Magnética funcional e Estimulação Magnética Transcraniana da intervenção única da Terapia Espelho em pacientes após Acidente Vascular Cerebral isquêmico

  • Leader : DRAULIO BARROS DE ARAUJO
  • MEMBRES DE LA BANQUE :
  • ANTÔNIO CARLOS DOS SANTOS
  • DRAULIO BARROS DE ARAUJO
  • CLAUDIA DOMINGUES VARGAS
  • Data: 24 août 2012


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  • Terapia Espelho (TE) vem sendo usada como uma ferramenta de reabilitação para várias doenças, incluindo o Acidente Vascular Cerebral (AVC). Embora alguns estudos tenham mostrado a sua eficácia clínica, pouco se sabe sobre seus mecanismos neurais. Baseado nisso, este estudo teve como objetivo avaliar por meio da Ressonância Magnética funcional (fMRI) e da Estimulação Magnética Transcraniana (TMS) a neuromodulação cortical promovida pela intervenção única da Terapia Espelho em pacientes acometidos por Acidente Vascular Cerebral. Quinze pacientes participaram de sessão única de trinta minutos de TE. Os dados de fMRI foram analisados bilateralmente nas seguintes regiões de interesse (ROI): Área Motora Suplementar (AMS), córtex pré-motor (PM), córtex motor primário (M1), córtex sensorial primário (S1) e Cerebelo. Em cada ROI, as mudanças na porcentagem de ocupação e os valores de beta foram avaliados. No TMS foi analisado o Potencial Evocado Motor (PEM) sobre o hot spot M1. Um aumento significativo na amplitude do PEM foi observado após a terapia no grupo (p<0,0001) e em 4 pacientes (p <0,05). Nos resultados da fMRI houve uma redução significativano percentual deocupação noPMe cerebelocontralateralàmão afetada(p <0,05). Além disso, foi observado aumento significativonos valores debetanas seguintes áreasmotoras contralaterais: AMS, Cerebelo,PM eM1(p <0,005) e diminuiçãosignificativa nas áreasmotoras ipsilaterais: PM e M1 (p < 0,001).Nas áreas sensoriais foi observada redução em S1bilateralmente(p <0,0005). Assim, nossos resultados indicam que intervençãoúnica de TE mudamarcadoresneurobiológicosem direção aopadrão observadoem indivíduos saudáveis.Além disso, as alterações nas áreas motoras do hemisfério contralateralsãoopostas asdo ladoipsilateral, sugerindo um aumento na homeostase do sistema.

     

5
  • THEMIS TAYNAH DA SILVA SANTANA
  • EFEITOS DA SINALIZAÇÃO VIA CREB SOBRE A SOBREVIÊNCIA E DIFERENCIAÇÃO NEURONAL

  • Leader : MARCOS ROMUALDO COSTA
  • MEMBRES DE LA BANQUE :
  • MARCOS ROMUALDO COSTA
  • LUCIANA DUARTE MARTINS DA MATTA
  • JOÃO RICARDO LACERDA DE MENEZES
  • Data: 21 sept. 2012


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  • Para que o desenvolvimento cortical ocorra normalmente, é preciso que haja um processo minuciosamente orquestrado de proliferação, migração e diferenciação dos neurônios recém-formados para, finalmente, se alcançar a elaboração de uma rede funcional. O padrão da arborização dendrítica define a eficácia com que a informação sináptica é transmitida ao soma; e a aquisição de uma morfologia dendrítica madura depende da ação coordenada de um número diverso de fatores. No sistema nervoso, fatores de transcrição como o CREB regulam uma ampla gama de processos incluindo crescimento e sobrevivência neuronal através da expressão de genes CREB-dependentes. A fosforilação de CREB e, portanto, sua ativação, ocorre por meio de várias vias de sinalização. Neste projeto, através do bloqueio de quatro diferentes kinases (PKA, CaMKII, MAPK e PI3K) procuramos identificar quais dessas cascatas de sinalização estariam envolvidas, por meio do CREB, na diferenciação e sobrevivência neuronal. Experimentos in vitro foram conduzidos com o uso de técnicas genéticas para expressar diferentes formas do CREB em neurônios corticais; o dominante negativo A-CREB e uma forma constitutivamente ativa do CREB, o CREB-FY. De forma geral, observamos que aspectos distintos do crescimento neuronal foram afetados pela inibição de cascatas específicas de sinalização. A inibição da PKA e da CAMKII diminuiu o comprimento dos processos neuronais, ao passo que a inibição da MAPK não afetou o comprimento, mas aumentou o numero de processos. O bloqueio da PI3K não pareceu alterar a morfologia neuronal, nem o tamanho do soma pareceu estar sob influência dessas proteínas kinases. Além disso, quando da expressão do A-CREB, uma diminuição significativa da sobrevivência neuronal foi observada a partir de 60h in vitro. Em conjunto, nossos dados indicam que a sinalização por CREB exerce influência sobre a morfologia de neurônios corticais, principalmente quando fosforilado pela PKA; e que o bloqueio da sinalização mediada por CREB prejudica a sobrevivência dessas células. Estes resultados contribuem para o entendimento do papel da sinalização por CREB ativado por diferentes vias sobre a sobrevivência e diferenciação neuronal e poderão ser de grande valia na elaboração de estratégias regenerativas em diferentes doenças neurológicas. 

     


6
  • KELLY SOARES FARIAS
  • INTERFERINDO COM OSCILAÇÕES DE ALTA FREQUÊNCIA NO HIPOCAMPO EPILÉPTICO: CONSEQUÊNCIAS PARA DAS CRISES ESPONTÂNEAS

  • Leader : CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
  • MEMBRES DE LA BANQUE :
  • MARCELO CAIRRÃO ARAUJO RODRIGUES
  • RODRIGO NEVES ROMCY PEREIRA
  • CLAUDIO MARCOS TEIXEIRA DE QUEIROZ
  • Data: 11 oct. 2012


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  • Crises epilépticas são desordens paroxísticas do sistema nervoso central (SNC) caracterizadas por uma descarga elétrica neuronal anormal, com ou sem perda de consciência e com sintomas clínicos variados. Nas epilepsias do lobo temporal as crises tem início focal, em estruturas do sistema límbico. Dados clínicos e experimentais mostram que essas regiões apresentam morte neuronal (esclerose hipocampal), reorganização sináptica (brotamento aberrante das fibras musgosas) e gliose reativa, sendo esses marcadores biológicos da zona epileptogênica. Registros extracelulares mostram que além das alterações anatômicas mencionadas acima, a zona epileptogênica também apresenta oscilações de alta frequência patológicas (pOAF). As pOAF são oscilações transientes (50 – 100 ms de duração), de baixa amplitude (200 µV - 1.5 mV) e de frequências variáveis (80 – 800 Hz). A relação entre essas oscilações e a gênese das crises espontâneas ainda é desconhecida. O objetivo do presente trabalho foi avaliar os efeitos da estimulação elétrica intracerebral (EIC) nas pOAF e frequência de crises espontâneas de animais cronicamente epilépticos (modelo da epilepsia do lobo temporal). Atualmente, a EIC é utilizada no tratamento de distúrbios do movimento (e.g., mal de Parkinson) e em alguns casos de dor crônica, e experimentalmente, no tratamento das epilepsias de difícil controle. A hipótese de trabalho dessa dissertação é de que a indução de depressão de longa duração por EIC, ao reduzir a excitabilidade neuronal local, modulará as pOAF, bem como a frequência de crises espontâneas. Para isso, comparamos as características espectrais das pOAF e a frequência de crises espontâneas antes e depois de um protocolo de 12 horas de estimulação elétrica de baixa frequência (0,2 Hz) aplicado na via perforante. De fato, esse protocolo reduziu a amplitude do potencial de ação coletivo registrado no giro denteado (GD) do hipocampo dorsal em 45% (amplitude média da primeira e da última hora de estimulação: 7,3 ± 3,0 mV e 4,1 ± 1,5 mV, respectivamente; p<0,05; teste T). O monitoramento contínuo do potencial de campo local, realizado no GD e em CA3 simultaneamente, mostrou que o protocolo de estimulação empregado foi eficaz em (i) aumentar a duração (64,6 ± 9,3 ms vs. 70,5 ± 11,5 ms) e reduzir (ii) a entropia (3,72 ± 0,28 vs. 3,58 ± 0,30), (iii) o índice pOAF (0,20 ± 0,08 vs. 0,15 ± 0,07) e (iv) o modo espectral (237,5 ± 15,8 Hz vs. 228,7 ± 15,2 Hz) das pOAF (valores do GD, expressos como média ± desvio-padrão, para os períodos “pré” e “pós” estimulação respectivamente; p<0,05; teste T). Ainda, este protocolo reduziu significativamente a frequência de crises espontâneas (1,8 ± 0,4 vs. 1,0 ± 0,3 crises/hora; “pré” e “pós” estimulação, respectivamente; p<0,05; teste T). Curiosamente, observamos um aumento na duração média das crises espontâneas após o término do protocolo (39,7 ± 6,0 vs. 51,6 ± 12,5 s; “pré” e “pós” estimulação respectivamente; p<0,05; teste T). Estes resultados sugerem que a redução da excitabilidade neuronal, por meio de protocolos de estimulação elétrica, reorganiza o perfil espectral das pOAF. Esse efeito foi acompanhado de redução na frequência de crises espontâneas. Apesar de preliminar, o presente trabalho contribui para o desenvolvimento de terapias baseadas em EIC para as epilepsias.


2011
Thèses
1
  • ROBSON SCHEFFER TEIXEIRA
  • CARACTERIZAÇÃO DOS ACOPLAMENTOS FASE-AMPLITUDE NA REGIÃO CA1 DO HIPOCAMPO

  • Leader : ADRIANO BRETANHA LOPES TORT
  • MEMBRES DE LA BANQUE :
  • DRAULIO BARROS DE ARAUJO
  • ADRIANO BRETANHA LOPES TORT
  • OLAVO BOHRER AMARAL
  • Data: 2 déc. 2011


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  • As oscilações cerebrais não são completamente independentes, mas capazes de interagir umas com as outras através de acoplamentos entre frequências (cross frequency coupling, doravante CFC) em pelo menos quatro diferentes modalidades: amplitude-amplitude, fase-fase (coerência), fase-frequência e fase-amplitude. Evidências recentes sugerem que não somente os ritmos per se, mas também as interações entre eles estão envolvidas na execução de tarefas cognitivas, principalmente aquelas que requerem atenção seletiva, transmissão de informações e consolidação de memórias. Estudos recentes propõem que oscilações gama alta (60 – 150 Hz) transferem informações espaciais do córtex entorrinal medial para a região CA1 do hipocampo através do acoplamento com a fase de teta (4 – 12 Hz). Apesar destas descobertas, entretanto, pouco se sabe sobre as características gerais dos CFCs em diversas regiões cerebrais. Neste trabalho, registramos potenciais de campo local usando matrizes de multieletrodos (microfios de tungstênio insulados por Teflon) implantadas no hipocampo dorsal para registro neural crônico. O acoplamento fase-amplitude foi avaliado por meio da análise de comodulogramas, uma ferramenta de CFC desenvolvida recentemente (Tort et al. 2008, Tort et al. 2010). Todas as análises de dados foram realizadas em MATLAB (MathWorks Inc). Descrevemos duas oscilações funcionalmente distintas dentro da faixa de frequência de gama, ambas acopladas ao ritmo teta durante exploração ativa e sono REM: uma oscilação com um pico de atividade em ~80 Hz e uma mais rápida centrada em ~140 Hz. As duas oscilações são diferencialmente moduladas pela fase de teta conforme a camada de CA1; o acoplamento teta-80 Hz é mais forte no stratum lacunosum-moleculare, enquanto que o acoplamento teta-140 Hz é mais forte no stratum oriens-alveus. Este perfil laminar sugere que a oscilação de 80 Hz origina-se das entradas do córtex entorrinal para as camadas profundas de CA1, e que a oscilação de 140 Hz reflete a atividade de CA1 em camadas superficiais. Ademais, nós mostramos que a oscilação de 140 Hz difere-se das oscilações ripples associadas com sharp-waves em diversos aspectos chave. Nossos resultados demonstram a existência de novas oscilações de alta frequência associadas à teta e sugerem uma redefinição das oscilações gama alta.

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