Neural pathway connectivity and discharge changes between M1 and STN in hemiparkinsonian rats

Alterations of electrophysiological activities, such as changed spike firing rates, reshaping the firing patterns, and aberrant frequency oscillations between the subthalamic nucleus (STN) and the primary motor cortex (M1), are thought to contribute to motor impairment in Parkinson's disease (PD). However, the alterations of electrophysiological characteristics of STN and M1 in PD are still unclear, especially under specific treadmill movement. To examine the relationship between electrophysiological activity in the STN-M1 pathway, extracellular spike trains and local field potential (LFPs) of STN and M1 were simultaneously recorded during resting and movement in unilateral 6-hydroxydopamine (6-OHDA) lesioned rats. The results showed that the identified STN neurons and M1 neurons exhibited abnormal neuronal activity after dopamine loss. The dopamine depletion altered the LFP power in STN and M1 whatever in rest or movement states. Furthermore, the enhanced synchronization of LFP oscillations after dopamine loss was found in 12–35 Hz (beta frequencies) between the STN and M1 during rest and movement. In addition, STN neurons were phase-locked firing to M1 oscillations at 12–35 Hz during rest epochs in 6-OHDA lesioned rats. The dopamine depletion also impaired the anatomical connectivity between the M1 and STN by injecting anterograde neuroanatomical tracing virus into M1 in control and PD rats. Collectively, impairment of’ electrophysiological activity and anatomical connectivity in the M1-STN pathway may be the basis for dysfunction of the cortico-basal ganglia circuit, correlating with motor symptoms of PD.