Differential encoding of mammalian proprioception by voltage-gated sodium channels.

Abstract

Animals requiring purposeful movement for survival are endowed with mechanoreceptors, called proprioceptors, that provide essential sensory feedback from muscles and joints to spinal cord circuits, which modulates motor output. Despite the essential nature of proprioceptive signaling in daily life, the mechanisms governing proprioceptor activity are poorly understood. Here, we identified nonredundant roles for two voltage-gated sodium channels (Na_Vs), Na_V1.1 and Na_V1.6, in mammalian proprioception. Deletion of Na_V1.6 in somatosensory neurons (Na_V1.6^cKO mice) causes severe motor deficits accompanied by loss of proprioceptive transmission, which contrasts with our previous findings using similar mouse models to target Na_V1.1 (Na_V1.1^cKO). In Na_V1.6^cKO animals, we observed impairments in proprioceptor end-organ structure and a marked reduction in skeletal muscle myofiber size that were absent in Na_V1.1^cKO mice. We attribute the differential contributions of Na_V1.1 and Na_V1.6 to distinct cellular localization patterns. Collectively, we provide evidence that Na_Vs uniquely shape neural signaling within a somatosensory modality.