# Axonal myelination of interneurons in cortex: functional significance and plasticity

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $346,105

## Abstract

Axonal myelination of interneurons in cortex: functional significance and plasticity
The speed and efficiency of impulse conduction in myelinated fibers is clearly fundamental to component
density and functional powers of the human nervous system. There is also growing evidence that changes in
myelination can have profound effects on the function of local brain circuits, including synchrony of neuronal
activity and the interaction of neural oscillators. Myelin is most often thought of in association with the
processes of long-axon projection neurons. But recently, we have discovered that the locally-projecting,
relatively short-axon inhibitory interneurons are a major source of myelinated axons within cortical gray matter,
in contrast to the myelin in white matter that forms almost exclusively on the axons of long-distance projecting
excitatory neurons. In particular, interneuronal myelin appears to be confined to interneurons containing the
protein parvalbumin.
Synaptic inhibition is a central feature of neuronal networks. In cortex, numerous types of inhibitory
interneurons participate in regulating the excitatory/inhibitory balance, in neuronal synchronization and cortical
rhythms generation, and in plasticity associated with experience and learning. Even though axonal myelination
defines crucial properties of neuronal transmission, it has not been specifically studied in cortical interneurons.
Furthermore, pathologies of both the cortical inhibitory circuitry and of myelin are associated with many
neurological and mental disorders, including multiple sclerosis, schizophrenia, and autism. Our present
knowledge of myelination in the cortical gray matter, and in particular the myelination of inhibitory axons, is
limited and certainly must be augmented if we are to conquer such devastating disorders.
This proposal is based on a novel combination of electrophysiology and array tomography that delivers
functional, structural and molecular data on individual neurons or pairs of synaptically connected neurons. The
project will begin by investigating myelinated axons of parvalbumin positive basket cells and correlating their
structural organization and molecular composition with the electrophysiological properties of their action
potential discharge and resulting synaptic transmission onto target pyramidal neurons. Once such a baseline
has been established, the contribution of axonal myelination of parvalbumin interneurons to the plasticity of
neuronal circuits will be assessed using barrel cortex sensory deprivation as a model. The project will conclude
with a study of the pathological changes of interneuronal myelination in a mouse model of multiple sclerosis.
This proposal will provide much needed data regarding the organization of myelin of cortical interneurons, the
functional consequences and the plasticity of this organization, and its potential role in multiple sclerosis.

## Key facts

- **NIH application ID:** 9898469
- **Project number:** 5R01NS094499-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Vernon Daniel MADISON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $346,105
- **Award type:** 5
- **Project period:** 2016-07-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9898469

## Citation

> US National Institutes of Health, RePORTER application 9898469, Axonal myelination of interneurons in cortex: functional significance and plasticity (5R01NS094499-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9898469. Licensed CC0.

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