Seminários em Neurociências

 

Sexta-feira 10/12/2010 14:30h Auditório do Centro de Pesquisa César Timo-Iaria

 

Brain-derived neurotrophic factor (BDNF) and pattern separation in the hippocampus

Dr. Pedro Bekinschtein

Department of Experimental Psychology and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK; Instituto de Biología Celular y Neurociencias “Prof. Eduardo de Robertis”, Facultad de Medicina-CONICET, Universidad de Buenos Aires, Buenos Aires Argentina

To allow similar episodes to be distinguished in memory, the brain must form distinct representations of events. The computational process for making representations for similar input patterns more orthogonal to and distinct from each other has been referred to as “pattern separation”. Recent studies have suggested that the brain region crucial for the process of spatial pattern separation is the dentate gyrus (DG) of the hippocampus.  It is largely unknown, however, what mechanisms and molecules underlie pattern separation.  Brain-derived neurotrophic factor (BDNF) is a small dimeric secretory protein with an important role in excitatory transmission and plasticity in the adult brain. Here we show that an increase in BDNF in the dentate gyrus is associated with exposure to landmarks delineating similar, but not dissimilar spatial locations within an open field.  In contrast, no changes in Zif268, another plasticity-related protein, were detected, and no changes in BDNF levels were found in other regions, for example CA1. We have also found that blocking BDNF activity and expression in the DG interferes with the consolidation or storage of similar, but not dissimilar memories for spatial locations.  Our results indicate that the expression of BDNF, possibly related to plasticity processes in the DG, may be important for the encoding and/or consolidation of overlapping spatial memory traces.

 

 

To keep in mind: neurobiological mechanisms involves in long-term memory persistence

Dr. Pedro Bekinschtein

Department of Experimental Psychology and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK; Instituto de Biología Celular y Neurociencias “Prof. Eduardo de Robertis”, Facultad de Medicina-CONICET, Universidad de Buenos Aires, Buenos Aires Argentina

Many memories may last only for a few hours, others can last for days and only a few will stay with us for an entire lifetime. Persistence is the most characteristic attribute of long-term memory (LTM). To understand the processes that underlie memory, we must comprehend how is it that memory traces persist despite the short-lived nature and rapid turnover of their molecular substrates. LTM formation, but not short-term memory requires a stabilization process named consolidation, which may last for a few hours depending on the species and task to be retained. At the cellular level, consolidation depends on the synthesis of new proteins in the brain, particularly in the hippocampus. However, once LTM is formed it would be no longer sensitive to interferences. In this work, we demonstrate that around 12 h after acquisition of a one-trial associative memory there is a previously unknown memory phase that is necessary for persistence, but not for LTM formation. This phase involves new protein synthesis and requires Brain-Derived Neurtotrophic Factor (BDNF) activity and expression in the hippocampus. Moreover, BDNF is capable of promoting persistence of a non-lasting LTM, transforming it into a persistent one if it is exogenously injected into the hippocampus during the critical period. BDNF is not only necessary but also sufficient to promote this memory phase, since it is able to reverse the amnesic effect of general inhibition of protein synthesis during this phase required for LTM persistence. Finally, the effect of BDNF on the maintenance of LTM in the hippocampus is dependent on ERK1/2 activation and involves the expression of immediate-early genes such as c-Fos and Zif268. Our results indicate that a late stabilization phase is specifically required for persistence but not for memory formation and that LTM maintenance for days might require recurrent rounds of protein synthesis and BDNF in the hippocampus.

 

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Notícia cadastrada em: 07/12/2010 09:36
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