# Elucidating learning-induced molecular signatures in hippocampal mature oligodendrocytes at single-cell and spatial resolution: Implications for hippocampal function

> **NIH NS R21** · UNIVERSITY OF IOWA · 2026 · $231,350

## Abstract

Project Summary/Abstract
Neuronal plasticity is fundamental for cognitive and behavioral processes. Emerging evidence has shed light on
the role of oligodendrocytes in regulating activity-dependent plasticity. Although primarily recognized for their role
in forming myelin, mature oligodendrocytes also perform additional metabolic functions that facilitate energy-
efficient and rapid saltatory conduction in white matter tracts across neuronal circuits. Although it is established
that myelin plasticity can influence neurophysiology and behavior, a comprehensive understanding of the
molecular mechanisms by which mature oligodendrocytes regulate hippocampal function remain elusive. Recent
reports have identified the presence of distinct mature oligodendroglial subtypes within the hippocampus that
differ in their transcriptomic profiles, topographical distribution, and myelination characteristics, and it is likely
that these mature oligodendroglial subclasses also exhibit differences in cell-type-specific and spatial molecular
signatures during long-term memory storage. Our preliminary findings provide evidence of rapid changes in
transcriptomic signatures in mature myelinating oligodendrocytes within the first hour after spatial learning, likely
reflecting myelin-independent aspects of mature oligodendroglial function. The rapid and dynamic changes
observed in the transcriptomic landscape, coupled with the diversity in mature oligodendroglial cell types,
necessitate a thorough molecular investigation to fully comprehend the role of these cells in hippocampal
function. This proposal aims to elucidate the molecular signatures of mature oligodendroglial subtypes at single-
cell and spatial resolution during memory consolidation and investigate the functional consequences of
manipulating mature oligodendroglial gene expression on activity-dependent oligodendroglial plasticity
underlying hippocampal memory consolidation. The research will be conducted in two aims. In Specifi

## Key facts

- **NIH application ID:** 11304963
- **Project number:** 1R21NS143268-01A1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** EDWIN TED G. ABEL
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NS
- **Fiscal year:** 2026
- **Award amount:** $231,350
- **Award type:** 1
- **Project period:** 2026-02-05T00:00:00 → 2028-01-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11304963

## Citation

> US National Institutes of Health, RePORTER application 11304963, Elucidating learning-induced molecular signatures in hippocampal mature oligodendrocytes at single-cell and spatial resolution: Implications for hippocampal function (1R21NS143268-01A1). Retrieved via AI Analytics 2026-07-07 from https://api.ai-analytics.org/grant/nih/11304963. Licensed CC0.

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