Optogenetic dissection of circuit mechanism underlying beta-oscillation expression in Parkinsonism
The basal-ganglia (BG) form a complex loop with the cortex and the thalamus that is involved in action selection and movement control. Synchronized oscillatory activities in BG neuronal circuits have been proposed to play a key role in coordinating information flow within this neuronal network. If synchronized oscillatory activities are important for normal motor function, their dysregulation in space and time could be truly pathological. Indeed, in Parkinson’s disease (PD), many studies have reported an abnormal increase in the expression level of neuronal oscillations contained in the beta (β) frequency range (15-30 Hz). These abnormal β oscillations have been proposed to be responsible for two motor symptoms of PD: akinesia and bradykinesia. However, which neuronal circuits generate these abnormal β oscillations that propagate through the entire BG loop is not known. The subthalamic nucleus (STN) is a key nucleus in BG that receives converging inputs from the motor cortex (mCx) and the external globus pallidus (GP). It has been proposed that the reciprocally connected STN-GP microcircuit could act as a pacemaker that generates pathological oscillatory activity in BG but it is difficult to rule out the influence of mCx in this generation mechanism. Here, we used a rat model of PD combined with in vivo electrophysiological recordings and optogenetic manipulations to directly dissect how selective control of mCx, STN and GP causally influence BG network dynamic at beta frequencies. Our data both challenge the implication of mCx and STN in the generation mechanisms of abnormal β-oscillations but highlight the central role of GP that is necessary and sufficient for the maintenance of synchronized β activities in dopamine-depleted state.