Corticospinal Circuits from the Sensory and Motor Cortices Differentially Regulate Skilled Movements through Distinct Spinal Interneurons

Little is known about the organizational and functional connectivity of the corticospinal (CS) circuits that are essential for voluntary movement. Here, we map the connectivity between CS neurons in the forelimb motor and sensory cortices and various spinal interneurons, demonstrating that distinct CS-interneuron circuits control specific aspects of skilled movements. CS fibers originating in the mouse motor cortex directly synapse onto premotor interneurons, including those expressing Chx10. Lesions of the motor cortex or silencing of spinal Chx10+ interneurons produces deficits in skilled reaching. In contrast, CS neurons in the sensory cortex do not synapse directly onto premotor interneurons, and they preferentially connect to Vglut3+ spinal interneurons. Lesions to the sensory cortex or inhibition of Vglut3+ interneurons cause deficits in food pellet release movements in goal-oriented tasks. These findings reveal that CS neurons in the motor and sensory cortices differentially control skilled movements through distinct CS-spinal interneuron circuits. [Display omitted] •Mouse CS axons from motor and sensory cortices project to distinct spinal regions•We map connectivity between CS neurons and various spinal interneurons•CS neurons in motor cortex control reaching via spinal Chx10+ interneurons•CS neurons in sensory cortex control food release via spinal Vglut3+ interneurons Ueno et al. generate a detailed connectivity map between corticospinal (CS) neurons in the motor and sensory cortices and spinal interneurons. The CS circuits originating from the motor and sensory cortices connect to distinct subpopulations of spinal interneurons to control discrete aspects of skilled movements.