Effect of Optogenetic Stimulation Parameters on Firing Rate of Basal Ganglia Neurons in Parkinsonian State BG and RT Networks

Abstract

Purpose: Parkinson's disease is a neurodegenerative disorder that affects the basal ganglia of the brain, which plays an important role in movement. Basal Ganglia-Thalamic network model including Subthalamic nucleus, Globus Pallidus externa, Globus Pallidus interna and Thalamus neurons. Optogenetics is a combination of optical and genetic tools used to stimulate basal ganglia neurons by light-sensitive ion channels (opsins) to eliminate the pathological effects of Parkinson's disease. Materials and Methods: To analyze the effect of optogenetic stimulation on Parkinsonian nervous systems, two complete models of BG and RT (including STN, GPe, Gpi, and TH neurons) have been selected and developed for Parkinson’s disease and to apply three and four-state optogenetic stimulation. For this purpose, ChETA, ChRwt, and NpHR opsins have been selected in three-state and four-state stimulations and different stimulation conditions according to different parameters in both models have been investigated. Results: To evaluate the performance of two models for each gene in three- and four-state stimulation conditions with different values of basic parameters, the value of error index is calculated and stimulation conditions that created an error index equal to zero have been introduced as optimal conditions. Based on the results, frequencies of 20 and 200 Hz in the four-state ChRwt model and frequency of 80 Hz in the three-state ChETA model have been introduced as optimal genes, frequencies, and models. To verify the developed model, the obtained results have been compared with the results of experimental studies. Conclusion: In optimal conditions, STN provides excitatory input and GPe provide appropriate inhibitory input to GPi, and GPi can provide appropriate inhibitory input to TH, and as a result, its function improves and pathological effects of Parkinson's disease disappear. The response of GPe neurons is consistent with the experimental results and the response of other neurons is also similar to the response of GPe neurons.

Keywords

• Parkinson’s Disease
• Optogenetic Stimulation
• Basal Ganglia Network Model
• Rubin-Terman Network Model