Sensorimotor circuits formed by dI3 neurons have distinct connectivity within and across the lumbar and cervical spinal cord.

Propriospinal interneurons in the spinal cord integrate multiple modalities of supraspinal and sensory inputs to modulate motor activity and facilitate complex motor behaviors, such as locomotion, skilled reaching, or grasping. The important ability of modulating motor activity in response to changes in the environment is partly mediated by a population of spinal interneurons marked by the expression Isl1, called dI3 neurons. These dI3 neurons are located throughout the cervical and lumbar spinal cord, receive cutaneous and proprioceptive feedback, and project to motoneurons. Previous work has demonstrated that dI3s are implicated in cutaneous-evoked reflexes and play a role in behaviors such as locomotion and grip strength, as well as motor recovery after spinal cord injury; however, it is unclear how different dI3 populations are connected to motor networks across the spinal cord to facilitate these diverse and complex functions. Through optogenetic activation of individual dI3 subpopulations located in different segments of the spinal cord, we mapped the functional connectivity of dI3 premotor circuits across the lumbar and cervical enlargements. We demonstrate that individual dI3 subpopulations have unique connectivity patterns and together form short and long propriospinal circuits that are either ipsilateral or commissural. Our findings suggest that dI3 subpopulations modulate the activity of distinct motor pools to differentially modulate complex motor functions such as grasping or locomotion.NEW & NOTEWORTHY We used an isolated mouse spinal cord preparation to optogenetically stimulate individual subpopulations of dI3 neurons. We investigated for the first time the specific connectivity patterns of dI3 neurons and demonstrated that they activate premotor circuits beyond their local segment, including short propriospinal, long propriospinal, and commissural circuits.