
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.27.609982
preprint
1
Article
Differential encoding of mammalian proprioception by voltage-gated sodium channels
Espino Cyrrus M. http://orcid.org/0000-0003-2708-4577

Nagaraja Chetan http://orcid.org/0000-0001-9768-9462

Ortiz Serena http://orcid.org/0000-0003-4872-1360

Dayton Jacquelyn R.
Murali Akash R. http://orcid.org/0000-0002-7696-0505

Ma Yanki http://orcid.org/0000-0002-6135-8298

Mann Emari L. http://orcid.org/0009-0000-5110-1555

Garlapalli Snigdha
Wohlgemuth Ross P. http://orcid.org/0000-0002-1841-2148

Brashear Sarah E. http://orcid.org/0000-0003-4601-3520

Smith Lucas R. http://orcid.org/0000-0002-7610-4231

Wilkinson Katherine A. http://orcid.org/0000-0002-2692-5533

Griffith Theanne N. http://orcid.org/0000-0003-0090-6286

28 8 2024
2024.08.27.609982https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.08.27.609982
nihpp-2024.08.27.609982.pdf
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 (NaV1.6 cKO 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 (NaV1.1 cKO ). In NaV1.6 cKO animals, loss of proprioceptive feedback caused non-cell- autonomous impairments in proprioceptor end-organs and skeletal muscle that were absent in NaV1.1 cKO 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.

Teaser

Voltage gated sodium channels differentially encode mammalian proprioception via distinct cellular localization patterns.
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pmc
