Characterization of propriospinal neurons in the mouse spinal cord

Abstract

The generation of movements is a fundamental function of the central nervous system. The neural circuits responsible for the execution of motor commands are distributed throughout the spinal cord and regulate the coordinated activation of multiple muscles across different joints and body regions, in response to motor and sensory stimuli. Therefore, effective communication between different spinal segments is essential for ensuring a synchronized motor performance. Recent studies have highlighted the importance of long-projecting spinal interneurons, known as propriospinal neurons (PN), in coupling distant spinal circuits to guarantee limb coordination and postural stability during locomotion. However, their subtype identity and precise functions are not yet completely understood. Here, we set out to systematically characterize PN from an anatomical, molecular, and functional perspective. First, by using rabies retrograde tracing, we studied the anatomical organization of ascending (a) and descending (d) PN. Second, we performed transcriptional analysis to reveal their molecular signatures. In particular, we characterized three different populations of aPN whose properties are consistent with two ventral cardinal interneuron subtypes (V0G and V3) and a specific subset of neurons expressing Sst, residing in a stereotyped and conserved position in the lateral deep dorsal horn. Finally, by taking advantage of the identified anatomical and molecular features, we designed intersectional strategies to unravel the functional roles of V0G and Sst+ aPN subtypes in vivo. Our results show that V0G aPN play a crucial role in modulating corrective motor reflexes, while Sst+ aPN appear to be involved in regulating sensorimotor integration. Taken together, our findings provide new insights into the anatomical and molecular diversity of PN subtypes and pave the way for future research into their functional significance for motor and sensorimotor control.