Abstract
Neural activity in the brain of parkinsonian patients is characterized by the intermittently synchronized oscillatory dynamics. This imperfect synchronization, observed in the beta frequency band, is believed to be related to the hypokinetic motor symptoms of the disorder. Our study explores potential mechanisms behind this intermittent synchrony. We study the response of a bursting pallidal neuron to different patterns of synaptic input from subthalamic nucleus (STN) neuron. We show how external globus pallidus (GPe) neuron is sensitive to the phase of the input from the STN cell and can exhibit intermittent phase-locking with the input in the beta band. The temporal properties of this intermittent phase-locking show similarities to the intermittent synchronization observed in experiments. We also study the synchronization of GPe cells to synaptic input from the STN cell with dependence on the dopamine-modulated parameters. Earlier studies showed how the strengthening of dopamine-modulated coupling may lead to transitions from non-synchronized to partially synchronized dynamics, typical in Parkinson's disease. However, dopamine also affects the cellular properties of neurons. We show how the changes in firing patterns of STN neuron due to the lack of dopamine may lead to transition from a lower to a higher coherent state, roughly matching the synchrony levels observed in basal ganglia in normal and parkinsonian states. The intermittent nature of the neural beta band synchrony in Parkinson's disease is achieved in the model due to the interplay of the timing of STN input to pallidum and pallidal neuronal dynamics, resulting in sensitivity of pallidal output to the phase of the arriving STN input. Thus the mechanism considered here (the change in firing pattern of subthalamic neurons through the dopamine-induced change of membrane properties) may be one of the potential mechanisms responsible for the generation of the intermittent synchronization observed in Parkinson's disease.
Highlights
A variety of oscillatory rhythms are widely observed in various neural systems from central pattern generators to human central nervous system [1]
Summary of the results Activity patterns in parkinsonian brain are characterized by intermittently synchronized oscillations within basal ganglia
Experimental and numerical studies have implicated that the subthalamic nucleus - external Globus Pallidus network may provide neural substrate for these characteristic oscillations within parkinsonian basal ganglia (BG)
Summary
A variety of oscillatory rhythms are widely observed in various neural systems from central pattern generators to human central nervous system [1]. We considered how dopamine-dependent features of STN neuronal firing modulate the GPe response and the synchrony between STN input and GPe output This simple network was able to demonstrate the overall transition from a low coherence state to a high coherence state through intermittent synchronous activity, as the STN activity pattern (influenced by changes in the STN properties modulated by dopamine) varies. These results support the important role of GPe cells within the BG circuit and demonstrate that the response of the GPe cell, which was achieved through the interaction between the intrinsic properties of GPe cells themselves and firing properties of STN cells, provide a logical explanation for the temporal characteristics of synchrony observed in experimental settings
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