# Cellular and molecular mechanisms of cold-adapted mechanosensation in the hibernating squirrel

> **NIH NIH F31** · YALE UNIVERSITY · 2024 · $48,974

## Abstract

PROJECT SUMMARY
 The thirteen-lined ground squirrel is an obligate hibernator that seasonally drops its body temperature from
37° in the active state to 2-4°C during torpor. While such temperatures typically inhibit peripheral signaling in
mammals, torpid squirrels remain sensitive to tactile cues and can be awakened by the sense of touch
(mechanosensation). However, the neurobiological mechanisms involved remain unknown. The long-term
goal of this study is to identify the cellular and molecular signatures that afford cold-resistant
mechanosensation to support extreme thermal tolerance in mammals.
 Pressure stimuli are sensed by a specialized subset of neurons in the dorsal root ganglion (DRG) known as
mechanoreceptors. Mechanically gated ion channels such as Piezo2 convert pressure into ionic current that
activates voltage-gated ion channels, which relay the signal downstream through action potentials (APs).
Piezo2 and voltage-gated ion channels have temperature-dependent dynamics ripe for evolutionary
manipulations permitting thermal resistance. This study, which will be conducted at the laboratories of Drs.
Elena Gracheva and Slav Bagriantsev at Yale University, assesses the central hypothesis that ion channel
modifications in mechanoreceptors underlie cold-adapted mechanosensation in the thirteen-lined ground
squirrel.
 Past work from the Gracheva and Bagriantsev labs has shown that this species shows constitutively low
thermosensitivity and decreased function of nociceptive AP machinery during torpor. Our preliminary work also
shows that mechanosensitive currents are preserved during torpor. Accordingly, we use a combination of in
situ hybridization, RNA sequencing and electrophysiology to assess whether squirrel DRG neurons have
selectively potentiated mechanosensitivity at the cost of other sensory modalities, relative to mouse
DRG neurons (Aim 1). Moreover, cold exposure widens APs and disrupts voltage gradients in typical
mammalian neurons due to slowed kinetics of the Na+/K+ ATPase pump. In contrast, our preliminary work
shows that cold-exposed torpid neurons show decreased AP widening and intact resting membrane potential.
In light of these data, we use whole-cell and ex vivo electrophysiology to assess whether squirrel
mechanoreceptors have cold-resistant electrogenic machinery (Aim 2).
 To the best of our knowledge, this study represents the first attempt to dissect cellular mechanisms of cold-
adapted mechanosensation in mammals. Elucidating neural function in extreme cold has the potential to
provide novel targets for combatting neuronal damage following clinical hypothermic procedures.

## Key facts

- **NIH application ID:** 10754246
- **Project number:** 5F31NS131036-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Rebecca Greenberg
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 5
- **Project period:** 2022-12-16 → 2025-10-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10754246

## Citation

> US National Institutes of Health, RePORTER application 10754246, Cellular and molecular mechanisms of cold-adapted mechanosensation in the hibernating squirrel (5F31NS131036-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10754246. Licensed CC0.

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