Differential encoding of mammalian proprioception by voltage-gated sodium channels

Espino, C. M.; Nagaraja, C.; Ortiz, S.; Dayton, J. R.; Murali, A. R.; Ma, Y.; Mann, E. L.; Garlapalli, S.; Wohlgemuth, R. P.; Brashear, S. E.; Smith, L. R.; Wilkinson, K. A.; Griffith, T. N.

doi:10.1101/2024.08.27.609982

bioRxiv · 10.1101/2024.08.27.609982

Differential encoding of mammalian proprioception by voltage-gated sodium channels

Espino, C. M.·Nagaraja, C.·Ortiz, S.·Dayton, J. R.·Murali, A. R.·Ma, Y.·Mann, E. L.·Garlapalli, S.·Wohlgemuth, R. P.·Brashear, S. E.·Smith, L. R.·Wilkinson, K. A.·Griffith, T. N.

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Abstract

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 (NaVs), NaV1.1 and NaV1.6, in mammalian proprioception. Deletion of NaV1.6 in somatosensory neurons (NaV1.6cKO mice) causes severe motor deficits accompanied by complete loss of proprioceptive transmission, which contrasts with our previous findings using similar mouse models to target NaV1.1 (NaV1.1cKO). In NaV1.6cKO animals, loss of proprioceptive feedback caused non-cell- autonomous impairments in proprioceptor end-organs and skeletal muscle that were absent in NaV1.1cKO mice. We attribute the differential contribution of NaV1.1 and NaV1.6 in proprioceptor function to distinct cellular localization patterns. Collectively, these data provide the first evidence that NaV subtypes uniquely shape neurotransmission within a somatosensory modality. TeaserVoltage gated sodium channels differentially encode mammalian proprioception via distinct cellular localization patterns.

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Espino, C. M., Nagaraja, C., Ortiz, S., Dayton, J. R., Murali, A. R., Ma, Y., Mann, E. L., Garlapalli, S., Wohlgemuth, R. P., Brashear, S. E., Smith, L. R., Wilkinson, K. A., Griffith, T. N.. 2024-08-28. Differential encoding of mammalian proprioception by voltage-gated sodium channels. https://doi.org/10.1101/2024.08.27.609982

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