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

TLDR

Little is known about the organizational and functional connectivity of corticospinal circuits essential for voluntary movement. The study aims to map the connectivity between corticospinal neurons in forelimb motor and sensory cortices and spinal interneurons to show that distinct CS–interneuron circuits govern specific aspects of skilled movements. Using anatomical tracing, the authors mapped connections from motor‑cortex CS neurons to premotor interneurons (including Chx10) and from sensory‑cortex CS neurons to Vglut3+ spinal interneurons. They found that motor‑cortex CS fibers directly synapse onto premotor Chx10 interneurons, and lesions or silencing of these interneurons impair skilled reaching, whereas sensory‑cortex CS neurons preferentially target Vglut3+ interneurons, and their lesions or inhibition disrupt food‑pellet release in goal‑oriented tasks, demonstrating that motor and sensory cortices differentially control skilled movements through distinct spinal interneuron circuits.

Abstract

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.