Model-based optogenetic stimulation to regulate beta oscillations in Parkinsonian neural networks

Optogenetic stimulation, an effective stimulation technique, is applied to the treatment of Parkinson’s disease (PD) to compete with the current neuromodulation technology that focuses on the electrical stimulation. Using the cortical-thalamic-basal ganglia model, we systematically study the effect of optogenetic stimulation on pathological parkinsonian rhythmic neural activity. Based on the experimental studies, four types of neurons are selected as stimulation targets. Our results indicate that both the optogenetic excitatory stimulation of D1 medium spiny neurons and inhibitory stimulation of globus pallidus internal (GPi) can directly suppress the abnormal discharge of GPi neurons. The former stimulation pattern drives the model to health state with smaller stimulation parameters, suggesting that inhibiting the GPi abnormal discharge through synaptic action seems to be more effective. Compared with electrical stimulation, it is found that 120Hz optogenetic excitatory stimulation does not accurately activate the action potential of subthalamic nucleus (STN). In contrast, only optogenetic excitatory stimulation of globus pallidus externa (GPe) can reduce the firing rate of STN and GPi simultaneously. Finally, we study the difference between the effects of high-frequency low pulse width stimulation and low-frequency high pulse width stimulation while maintaining the same pulse duty cycle. For GPe, different stimulation patterns play a positive role as long as the stimulation frequency is not in the beta-band. Although the feasibility of optogenetic stimulation remains to be clinically explored, the results obtained help us understand the pathophysiology of PD.