# Axonal signaling regulating oligodendrocyte differentiation

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2024 · $444,599

## Abstract

Abstract
 The current studies are based on unexpected data from early brain development in mice establishing that
reduced neuronal activity results in premature oligodendrocyte progenitor cell differentiation. These data
contrast with the extensive data in the literature that axonal activity increases myelination. The fundamental
hypothesis under investigation is that during early development, neuronal activity initially allows and/or
enhances OPC proliferation but inhibits premature differentiation. The current studies will use Designer
Receptors Exclusively Activated by Designer Drugs (DREADD)-expression in cortical neurons to investigate
the impact of decreased or increased neuronal activity on oligodendrocyte progenitor cell proliferation, survival
and differentiation in corpus callosum and cortex. scRNASeq studies will characterize the transcriptome
changes in oligodendrocyte progenitor cells when cortical neuronal activity is reduced or increased. Our data
establishing that reduced neuronal activity induces premature oligodendrocyte differentiation in young mice are
unexpected given the significant data in the literature establishing that neuronal activity enhances
oligodendrocyte progenitor cell differentiation and myelination later in development. We will therefore
investigate when during development the impact of neuronal activity shifts from blocking differentiation to
enhancing differentiation.

## Key facts

- **NIH application ID:** 10986671
- **Project number:** 1R21NS135041-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** WENDY B MACKLIN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $444,599
- **Award type:** 1
- **Project period:** 2024-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10986671

## Citation

> US National Institutes of Health, RePORTER application 10986671, Axonal signaling regulating oligodendrocyte differentiation (1R21NS135041-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10986671. Licensed CC0.

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