Dopaminergic modulation of primary motor cortex: From cellular and synaptic mechanisms underlying motor learning to cognitive symptoms in Parkinson's disease.

The primary motor cortex (M1) is crucial for movement execution, especially dexterous ones, but also for cognitive functions like motor learning. The acquisition of motor skills to execute dexterous movements requires dopamine-dependent and -independent plasticity mechanisms within M1. In addition to the basal ganglia, M1 is disturbed in Parkinson's disease (PD). However, little is known about how the lack of dopamine (DA), characteristic of PD, directly or indirectly impacts M1 circuitry. Here we review data from studies of PD patients and the substantial research in non-human primate and rodent models of DA depletion. These models enable us to understand the importance of DA in M1 physiology at the behavioral, network, cellular, and synaptic levels. We first summarize M1 functions and neuronal populations in mammals. We then look at the origin of M1 DA and the cellular location of its receptors and explore the impact of DA loss on M1 physiology, motor, and executive functions. Finally, we discuss how PD treatments impact M1 functions.

Dopamine D2-Like Receptors Modulate Intrinsic Properties and Synaptic Transmission of Parvalbumin Interneurons in the Mouse Primary Motor Cortex.

Dopamine (DA) plays a crucial role in the control of motor and higher cognitive functions such as learning, working memory, and decision making. The primary motor cortex (M1), which is essential for motor control and the acquisition of motor skills, receives dopaminergic inputs in its superficial and deep layers from the midbrain. However, the precise action of DA and DA receptor subtypes on the cortical microcircuits of M1 remains poorly understood. The aim of this work was to investigate in mice how DA, through the activation of D2-like receptors (D2Rs), modulates the cellular and synaptic activity of M1 parvalbumin-expressing interneurons (PVINs) which are crucial to regulate the spike output of pyramidal neurons (PNs). By combining immunofluorescence, ex vivo electrophysiology, pharmacology and optogenetics approaches, we show that D2R activation increases neuronal excitability of PVINs and GABAergic synaptic transmission between PVINs and PNs in Layer V of M1. Our data reveal how cortical DA modulates M1 microcircuitry, which could be important in the acquisition of motor skills.