# The electrical basis of proprioceptive signaling

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $491,757

## Abstract

Project Summary. Our ability to internally sense body and limb position, referred to as proprioception, is
essential for purposeful movement and is known to be impaired in a variety of conditions such as amyotrophic
lateral sclerosis, peripheral neuropathy, and aging. Conversely, activation of peripheral proprioceptive pathways
promotes recovery from spinal cord injury, highlighting the translational relevance of understanding how
proprioception is encoded. Proprioceptors, the sensory neurons that initiate proprioceptive signaling, require
Piezo2 to transduce muscle movement into electrical signals for normal motor function. What happens
downstream of Piezo2 activation is debated. We will address a fundamental yet unanswered question in the field
of sensory-motor neuroscience: how do voltage- gated sodium channels (NaVs) shape proprioceptor function in
sensory-motor circuits? Mammalian proprioceptors express three NaVs: NaV1.1, NaV1.6, and NaV1.7. Our lab
has published the only functional evidence to date on the contributions of any NaV to mammalian proprioception.
Because the genetic access point to proprioceptors is parvalbumin, a protein also expressed in brain and spinal
cord neurons, we used a sensory-neuron wide genetic targeting strategy that spares the confounding factors
associated with NaV deletion in the central nervous system. We reported that loss of the NaV1.1 isoform results
in inconsistent proprioceptor coding of sustained muscle stretch and visible motor behavior deficits. Our new
pilot data support the notion that while NaV1.1 is tasked with maintaining reliable proprioceptive transmission,
the NaV1.6 isoform is tasked with initiating proprioceptive signaling. The role of NaV1.7 in shaping proprioceptive
signaling remains unknown and will be directly investigated for the first time in this proposal. We will leverage
inducible conditional knockout mouse models to systematically delete individual Navs after proprioceptor
development and investigate how NaV1.1, NaV1.6, and NaV1.7 distinctly contribute to mammalian proprioception.
Using a combination of behavior and mechanistic in vitro patch-clamp electrophysiological experiments, we aim
to determine how acute disruption of NaV expression post-weaning impacts motor behaviors, and will also identify
NaV subtype-specific biophysical features that govern proprioceptor excitability. These studies will be
complemented by quantitative immunohistochemistry and super-resolution imaging to identify the cellular
localization of each NaV isoform within proprioceptors. We will also use ex vivo muscle-nerve recordings and
optogenetics to define how NaVs expressed in proprioceptors individually shape peripheral neurotransmission,
which will inform interpretation of our behavioral analyses. Finally, we will determine which NaVs are essential
for proprioceptor synaptic transmission in central circuits using two different ex vivo spinal cord electrophysiology
preparations. Collectively, this work w...

## Key facts

- **NIH application ID:** 10979054
- **Project number:** 1R01NS135005-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Theanne Nicole Griffith
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $491,757
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10979054

## Citation

> US National Institutes of Health, RePORTER application 10979054, The electrical basis of proprioceptive signaling (1R01NS135005-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10979054. Licensed CC0.

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