January 2025
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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.