Differential encoding of mammalian proprioception by voltage-gated sodium channels | Science Advances

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 _V s), Na _V 1.1 and Na _V 1.6, in mammalian proprioception. Deletion of Na _V 1.6 in somatosensory neurons (Na _V 1.6 ^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 _V 1.1 (Na _V 1.1 ^cKO ). In Na _V 1.6 ^cKO animals, we observed impairments in proprioceptor end-organ structure and a marked reduction in skeletal muscle myofiber size that were absent in Na _V 1.1 ^cKO mice. We attribute the differential contributions of Na _V 1.1 and Na _V 1.6 to distinct cellular localization patterns. Collectively, we provide evidence that Na _V s uniquely shape neural signaling within a somatosensory modality.