Optogenetic stimulation of primary motor cortex regulates beta oscillations in the basal ganglia: A Computational study

The primary motor cortex (M1) contains interconnected and diverse layers that play an important role in motor execution. In recent years, M1 has emerged as one of the hot targets for optogenetic stimulation in the treatment of Parkinson’s disease (PD). In this paper, we explore potential optogenetic stimulation targets in M1 based on the M1-basal ganglia–thalamus network model. The results show that excitatory optogenetic stimulation of layer 5 pyramid-tract (PT) neurons effectively activates hyper-direct pathways, which disrupts synchronous bursting behavior within the basal ganglia and reduces beta oscillations in globus pallidus pars interna (GPi). Upon this, we propose a new stimulation strategy that combines the stimulation of layer 5A intratelencephalic (IT) neurons and layer 5 PT neurons. We find that simultaneous excitation of IT neurons in layer 5A and inhibition of PT neurons effectively activates direct pathways and reduces abnormal beta oscillations within the GPi. Finally, we analyze the excitatory optogenetic stimulation of somatostatin (SOM) interneurons in the M1. Excitation of SOM neurons in layer 5 can inhibit PT and IT neurons in layer 5, thereby reducing beta oscillations in GPi via direct pathways, while excitatory stimulation of SOM neurons in layer 2/3 is ineffective. Overall, these results theoretically demonstrate that these three optogenetic stimulation strategies all have an inhibitory effect on abnormal rhythmic oscillations in PD.