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

Animals that require purposeful movement for survival are endowed with mechanosensory neurons 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 have identified distinct and nonredundant roles for two voltage-gated sodium channels (Nas), Na1.1 and Na1.6, in mammalian proprioception. Deletion of Na1.6 in somatosensory neurons (Na1.6 mice) causes severe motor deficits accompanied by complete loss of proprioceptive transmission, which contrasts with our previous findings using similar mouse models to target Na1.1 (Na1.1). In Na1.6 animals, loss of proprioceptive feedback caused non-cell-autonomous impairments in proprioceptor end-organs and skeletal muscle that were absent in Na1.1 mice. We attribute the differential contribution of Na1.1 and Na1.6 in proprioceptor function to distinct cellular localization patterns. Collectively, these data provide the first evidence that Na subtypes uniquely shape neurotransmission within a somatosensory modality.