# The Roles of Neuronal Activity in Peripheral Nerve Myelination

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $509,058

## Abstract

Project Summary
Myelination is critical for normal conduction of action potentials and synchronized transmission of neural
impulses. Recent studies have demonstrated that CNS myelin development, maturation and maintenance are
regulated by neuronal activity and experience. In contrast, very little is known about how experience and
activity regulate myelin development in the PNS, nor how experience-dependent neural activity affects re-
myelination after peripheral nerve or glial cell injury in vivo. This is in part due to the difficulty in precisely
altering activity of PNS nerves, since they are typically a mixture of both sensory and motor fibers, or of
sensory axons mediating different types of modalities. We hypothesize that sensory activity regulates
peripheral nerve myelination, myelin maintenance and remyelination, and propose to address this fundamental
gap in knowledge using the auditory system as a model. Type I auditory nerve (AN) fibers in the mouse
cochlea offer an ideal platform to dissect the role of activity on peripheral myelination because: (a) maturation
of AN myelin coincides with auditory function maturation during the first postnatal month, suggesting that
activity may affect Schwann cells; (b) re-myelination of AN fibers occurs following Schwann cell ablation; (c)
AN myelin dysfunction is associated with hearing deficits, demonstrating a critical role for myelination in
cochlear function, particularly in the transmission of key temporal features of sound that are important for
understanding speech; (d) we can manipulate the activity of primary auditory neurons by ablating hair cells, by
exposing animals to defined auditory experiences, or using genetic tools; (e) we can efficiently isolate and
examine the entire peripheral AN at the structural, cellular and molecular levels; and (f) we can assess the
impact of myelin defects on cochlear and auditory nerve function in the intact mouse can be assessed at high-
resolution with standard electrophysiological techniques. Furthermore, AN axons are myelinated by both
Schwann cells (in the distal part) and oligodendrocytes (in the proximal part), permitting a direct comparison of
the effects of activity on both types of myelinating cells within the same nerve. We will use mouse models to
address this gap in knowledge in three specific aims. In Aim 1, we will use mutants that are defective in hair
cell mechanotransduction and synaptic function to determine the role of AN activity in myelination during the
neonatal and juvenile time periods. In Aim 2, we will test the roles of auditory experience and NRG1/ErbBR
signaling in AN myelination during the neonatal and juvenile periods. Finally, in Aim 3, we will test whether
sound-driven neuronal activity modulates AN re-myelination in the mature cochlea. Successful completion of
the proposed aims will provide valuable insight into the role of neural activity in PNS myelination and a more
precise understanding of the impact of myelin dysfunct...

## Key facts

- **NIH application ID:** 10375469
- **Project number:** 5R01DC018500-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Gabriel Corfas
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $509,058
- **Award type:** 5
- **Project period:** 2020-04-20 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375469

## Citation

> US National Institutes of Health, RePORTER application 10375469, The Roles of Neuronal Activity in Peripheral Nerve Myelination (5R01DC018500-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10375469. Licensed CC0.

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