Loss of Midbrain Dopamine Neurons Does Not Alter GABAergic Inhibition Mediated by Parvalbumin-Expressing Interneurons in Mouse Primary Motor Cortex.

Abstract

The primary motor cortex (M1) integrates sensory and cognitive inputs to generate voluntary movement. Its functional impairments have been implicated in the pathophysiology of motor symptoms in Parkinson's disease (PD). Specifically, dopaminergic degeneration and basal ganglia dysfunction entrain M1 neurons into the abnormally synchronized bursting pattern of activity throughout the cortico-basal ganglia-thalamocortical network. However, how degeneration of the midbrain dopaminergic neurons affects the anatomy, microcircuit connectivity, and function of the M1 network remains poorly understood. The present study examined whether and how loss of dopamine (DA) affects the morphology, cellular excitability, and synaptic physiology of layer 5 parvalbumin-expressing (PV+) cells in the M1 of mice of both sexes. Here we reported that loss of midbrain dopaminergic neurons does not alter the number, morphology, and physiology of layer 5 PV+ cells in M1. Moreover, we demonstrated that the number of perisomatic PV+ puncta of M1 pyramidal neurons as well as their functional innervation of cortical pyramidal neurons were not altered following the loss of DA. Together, the present study documents an intact GABAergic inhibitory network formed by PV+ cells following the loss of midbrain dopaminergic neurons.Significance statement The pyramidal neurons in the motor cortex manifests highly synchronized bursting pattern of activity in parkinsonian state, but the underlying circuit mechanisms are poorly understood. One can easily consider PV interneurons-mediated inhibitory network as a potential microcircuitry mechanism. However, whether loss of DA affects cortical PV+ network remains unknown. The present work documented that loss of DA in parkinsonian state does not alter the number, morphology, cellular excitability, and synaptic physiology of PV+ cells in M1. An intact robust PV+ perisomatic inhibition of pyramidal neurons provides a microcircuit substrate for thalamic afferents to entrain cortical neurons to pathological oscillations throughout the cortico-basal ganglia-thalamocortical network in parkinsonian state.