Molecularly diverse glycinergic interneurons in the medial deep dorsal horn are interposed between primary sensory afferents and spinal Shox2 interneurons.

Abstract

Appropriate transmission of sensory afferent input from the peripheral nervous system to spinal locomotor circuits is crucial for efficient and adaptive locomotion. This is partly mediated by spinal interneurons (INs) that regulate afferent input relayed to locomotor networks. After a spinal cord injury (SCI), sensory afferent feedback becomes critical for motor recovery, however these pathways undergo plasticity. Previously, we observed a loss in the inhibitory sensory afferent pathway to locomotor rhythm generating Shox2 INs after SCI. Importantly, the inhibitory INs within sensory afferent pathways to Shox2 INs have yet to be defined. Thus, the goal of the present study was to identify inhibitory INs interposed between sensory afferents and Shox2 INs in the uninjured mouse. Using electrophysiology and pharmacology to test for connectivity, we demonstrate that lumbar inhibitory INs within sensory afferent pathways to Shox2 INs are glycinergic (GlyT2) INs in the medial deep dorsal horn. Afferent stimulation evoked currents in medial deep dorsal GlyT2 INs that were mostly from excitatory, putative monosynaptic connections. Consistent with the electrophysiology, parvalbumin⁺ afferent fibers densely innervated the region containing the medial deep dorsal GlyT2 INs. Additionally, the medial deep dorsal GlyT2 INs expressed multiple previously described deep dorsal horn molecular markers. These results identify an inhibitory sensory afferent pathway to Shox2 INs comprised of a molecularly diverse population of GlyT2 INs that may be important for the regulation of low-threshold afferent input to the spinal locomotor network.