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 (D2R), 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.

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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 how DA, through the activation of D2 receptors (D2R), 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 a mechanism through which cortical DA modulates M1 microcircuitry and might participate in the acquisition of motor skills.Significance StatementPrimary motor cortex (M1), which is a region essential for motor control and the acquisition of motor skills, receives dopaminergic inputs from the midbrain. However, precise action of dopamine and its receptor subtypes on specific cell types in M1 remained poorly understood. Here, we demonstrate in M1 that dopamine D2 receptors (D2R) are present in parvalbumin interneurons (PVINs) and their activation increases the excitability of the PVINs, which are crucial to regulate the spike output of pyramidal neurons (PNs). Moreover the activation of the D2R facilitates the GABAergic synaptic transmission of those PVINs on layer V PNs. These results highlight how cortical dopamine modulates the functioning of M1 microcircuit which activity is disturbed in hypo- and hyperdopaminergic states.