# The role of myelination in cortical circuit function and motor behavior

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $392,264

## Abstract

Nearly 1 million people in the United States alone are affected by Multiple Sclerosis (MS). MS is an
inflammatory, demyelinating disease of the central nervous system (CNS). While MS is classically regarded as
a disease of the white matter, the number of white matter lesions does not correlate with physical disability or
cognitive impairment. Recent evidence indicates that gray matter areas have significant myelin loss and
increased cortical lesion load is associated with increased cortical atrophy and cognitive decline. Functional
imaging of patients with MS reveals increased hyperexcitability within primary motor cortex and throughout the
motor network. Moreover, functional recovery in MS patients is associated with normalization of aberrant
cortical activity, suggesting a relationship between motor network hyperexcitability and impaired motor
behavior. However, our understanding of how myelin loss influences the activity of single neurons, or neural
circuits, within grey matter is extremely limited. Outstanding questions such as, what are the consequences of
demyelination on neural physiology in the intact CNS, how demyelinating injuries affect the acquisition of new
skills, and can therapies that can enhance remyelination can restore neural and behavioral function remain
unknown. Recently, we have developed new approaches to visualize myelin, oligodendrocytes, and their
precursors in the intact mouse brain, as well as longitudinal approaches to record and monitor neural activity in
behaving animals. We have also identified novel behavioral interventions that enhance myelin repair. In this
application, we propose to capitalize on the dynamics revealed by these techniques to discern the effects of
myelin loss and repair on local circuit activity and motor behavior. The objectives of this proposal are: 1)
evaluate how myelin loss affects neuronal circuit function and 2) to elucidate the effectiveness of remyelination
therapies on restoring neural function and behavior. This proposal will demonstrate the effects of demyelination
on cortical neuronal and circuit function in vivo. These studies will validate an in vivo mouse model platform to
test efficacy of new therapeutic candidates for MS, and provide clinically relevant data regarding the efficacy of
therapies that stimulate endogenous remyelination in MS on restoring neural and behavioral function.

## Key facts

- **NIH application ID:** 10087980
- **Project number:** 5R01NS115975-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Ethan Garrett Hughes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $392,264
- **Award type:** 5
- **Project period:** 2020-02-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10087980

## Citation

> US National Institutes of Health, RePORTER application 10087980, The role of myelination in cortical circuit function and motor behavior (5R01NS115975-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10087980. Licensed CC0.

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