Investigation of the origin of the β-band in Parkinson's disease in the basal ganglia circuitry: A neuronal analysis
synaptic and ephaptic.
beta$-band origin; Parkinson's Disease; Hodgkin-Huxley model; Ephaptic Communication.
Basal ganglia dysfunction is implicated in the pathogenesis of Parkinson's disease, manifested by alterations in firing
rate and excessive oscillations in the $\beta$ band (13-30 Hz). However, the mechanisms underlying these neural features
remain unclear. Empirical studies and neural network simulations suggest that dopamine depletion plays a significant role in
altering neural dynamics and increasing beta oscillations. Many studies, however, assume a homogeneous neuronal population
in the Globus Pallidus Externus (GPe). Furthermore, in silico studies have not adequately investigated the possible cellular
degeneration caused by the misfolded alpha-synuclein protein, which contributes to cell membrane degeneration and changes
in electrophysiological dynamics in Parkinson's disease. This study proposes that GPe neurons are impacted by the deposition
of misfolded alpha-synuclein, resulting in changes in the cellular structure and electrophysiological properties of the
membrane, which leads to a modified resonant oscillatory response in response to synaptic inputs and modulatory ephaptic
fields. This neural dysfunction stiffens the natural resonant process of neurons in the beta band, a characteristic of advanced
stages of Parkinson's disease. To test this hypothesis, a Hodgkin-Huxley-type model will be built with four distinct types of
neurons, representing the main electrophysiological characteristics of GPe neurons. In addition, neuronal degenerations will be
simulated based on empirical data and ion channel expressions observed in Parkinson's disease, mimicking the impact of
$\alpha$-synuclein on the neuronal membrane. Communication via electric fields (ephapticity), in addition to synaptic
communication, will be considered to evaluate their impact on the alteration of the dynamic regime. Preliminary results are
expected to demonstrate a resonance of the model in the beta band frequency range, initiated by specific types of GPe neurons
and leading to an anomalous synchronous process throughout the GPe, suggesting the origin of dysfunctional beta oscillations
due to ephaptic modulation between dysfunctional neurons caused by Parkinson's.