# Neuronal activity-dependent intracellular calcium signaling regulates oligodendrocyte maturation

> **NIH NIH F31** · UNIVERSITY OF COLORADO DENVER · 2023 · $9,049

## Abstract

PROJECT SUMMARY/ABSTRACT
Myelination is essential for information transfer and circuit function in the brain. New oligodendrocytes are
continuously generated throughout life, and recent studies showed that blocking the generation of new
oligodendrocytes disrupts learning and memory consolidation. Mature oligodendrocytes differentiate from
oligodendrocyte precursor cells (OPCs), a population of motile, proliferative precursors that tiles the CNS and
persists throughout life. OPCs receive direct synapses from neurons, and it has been hypothesized that they
integrate neuronal firing information to regulate their differentiation and myelination. Significant research has
been aimed at understanding the intracellular signaling pathways that regulate the maturation of
oligodendrocyte lineage cells (oligodendroglia), yet molecular mechanisms underlying neuronal activity-
dependent myelination are unknown. Furthermore, little is known about the excitation-transcription coupling
events that link extracellular neuronal stimulation with intracellular signaling dynamics and gene expression
changes in oligodendroglia. Activity-dependent changes in intracellular calcium drive myriad processes in
neurons related to synaptic plasticity and learning, yet the effects of calcium dynamics in OPCs have not been
carefully studied. Here, I will test the hypothesis that changes in neuronal activity modulate OPC calcium
release from intracellular stores to control their differentiation following learning. Aim 1 uses fast in vivo time
lapse imaging combined with viral expression of neurotoxins and holographic optogenetic stimulation to test
how manipulations in neuronal firing modulate OPC calcium signaling. Aim 2 combines in vitro molecular
biochemistry with longitudinal imaging and behavioral assays to assess if activity-dependent calcium release
from intracellular stores drives oligodendrogenesis. Results from these studies will provide essential insights
into the neuron-oligodendroglia interactions that govern myelin plasticity and may uncover novel therapeutic
targets for the treatment of demyelinating diseases.

## Key facts

- **NIH application ID:** 10646397
- **Project number:** 5F31NS120540-03
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Michael A Thornton
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $9,049
- **Award type:** 5
- **Project period:** 2021-07-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10646397

## Citation

> US National Institutes of Health, RePORTER application 10646397, Neuronal activity-dependent intracellular calcium signaling regulates oligodendrocyte maturation (5F31NS120540-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10646397. Licensed CC0.

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