# Genetic profiles and physiological heterogeneity of oligodendrocytes

> **NIH NIH R21** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2020 · $389,655

## Abstract

Project summary/Abstract
Oligodendrocytes (OLs) support neurons through the production of myelin. OLs were considered to be a
homogenous population programmed to passively myelinate axons. However, recent studies indicate that
OLs are a heterogeneous population with a subset of OLs that are able to detect and respond to neuronal
activity. To understand OL heterogeneity, it is necessary to resolve variations in gene expression that specify
the physiological functions of unique OL subpopulations. Our long-term goal is to determine the genetic
profiles corresponding to functional characteristics of the heterologous OL population, which will eventually
elucidate the diverse roles of OL subpopulations during development and disease. The ability to classify
discrete subtypes of OL will enhance our perspective of the role of cellular diversity in neural organization,
function, and disease.
 OLs respond to neuronal activity and support neuronal function through adaptive myelination that
shapes circuit timing to meet functional requirements and contributes to nervous system plasticity. OLs
display differential physiological profiles with differential responses to neuronal activity. However, the
mechanisms whereby OLs integrate neuronal signals to drive myelination remain unclear. Our recent studies
identified a novel excitable OL that conducts functional voltage-activated Na+ channel (Nav) currents sufficient
to evoke action potentials, and displays a Ca2+ response to neuronal activity in the brainstem. The objective
of the proposed study is to determine the molecular signature of excitable OLs for distinguishing them from
non-excitable OLs, and to investigate the presence of excitable OLs in other brain areas beyond the
brainstem. We hypothesize that Nav channel expression in OL lineage cells distinguishes an excitable
subpopulation of OLs with unique responses to neural activity and a distinct function in the developing brain.
To test the hypothesis we will use the innovative technique incorporating patch-clamp recording and single
cell RNA analysis from the same cells, which is referred to patch-seq transcriptomics. Aim 1 will characterize
the physiological and genetic profiles of excitable and non-excitable OLs using patch-seq. Aim 2 will identify
the presence of excitable OL in other brain areas, and compare their genetic and physiological profiles with
excitable OLs in the brainstem. The findings will provide novel insights on excitable oligodendroglia that
govern neuron-glia communication and adaptive myelination, and will expand our understanding of the
mechanisms that controls myelin growth, stability, and repair in the developing and adult brain.

## Key facts

- **NIH application ID:** 10058072
- **Project number:** 1R21NS116573-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Jun Hee Kim
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $389,655
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10058072

## Citation

> US National Institutes of Health, RePORTER application 10058072, Genetic profiles and physiological heterogeneity of oligodendrocytes (1R21NS116573-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10058072. Licensed CC0.

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