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

> **NIH NIH R56** · STANFORD UNIVERSITY · 2022 · $551,280

## Abstract

ABSTRACT
Parvalbumin-containing (PV+) fast spiking basket cells comprise an important subset of interneurons in the
brain. Cortical PV+ basket cells regulate the activity of principal pyramidal neurons and other interneurons to
influence a variety of behaviors. Diminished PV+ activity in cortex is associated with numerous psychiatric
disorders, including schizophrenia and other dissociative disorders, and autism. We propose to investigate the
properties of PV+ interneurons and their influence on their postsynaptic targets by focusing on the smallest
element of a neural circuit, the synaptic connection between two single neurons. We will apply a multipronged
approach by combining electrophysiological recordings from two synaptically connected neurons, with single
cell transcriptomic analysis of both neurons and high-resolution array tomographic reconstruction of the
anatomy of their synaptic connectivity. In these studies, the presynaptic neuron will be a PV+ basket cell, with
the postsynaptic partner being a pyramidal neuron or another interneuron. We propose three specific aims to
study the function and structure of the axon-myelin unit of PV+ interneurons within this quantal element of the
neural circuitry. 1) We will elucidate the rules of PV+ interneuron connectivity in the adult neocortex by
comparing the physiological and anatomical properties of the synaptic connections between individual
neurons (PV+ presynaptic), including synaptic strength, latency, and failure rate, the directionality of activity-
induced plasticity, as well as the number of synapses created between the two neurons, the number of
connecting axon paths, length and thickness of axon paths and the extent of axon myelination. 2) We will
characterize the synapses that PV+ basket cells project onto different compartments of the postsynaptic
neuron, and specifically the much less understood PV+ synapses onto distal dendrites and spines, including
their axonal paths and synaptic molecular content, comparing those to soma-directed synapses. In the case of
spine synapses we will also clarify the identity of the excitatory synapse onto the same spine. 3) We will study
the gene expression in PV+ interneurons and in their postsynaptic target neurons with single cell RNA-seq,
and correlate gene expression patterns with the electrophysiological properties of synaptic transmission and
synaptic plasticity, and with the morphological characteristics of these synaptic connections revealed by 3D
reconstruction by array tomography, including, but not limited to myelination, axonal path length, number of
synapses, and their molecular character. By elucidating the function of PV+ cells and their myelinated axon in
the smallest neural circuit interaction, we aim to gain insight into how these crucial elements of brain circuits
contribute to normal and pathological brain function, thus providing the knowledge base needed for improved
treatment design for PV+ interneuron-related disorders.

## Key facts

- **NIH application ID:** 10626677
- **Project number:** 2R56NS094499-06A1
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Vernon Daniel MADISON
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $551,280
- **Award type:** 2
- **Project period:** 2022-08-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10626677

## Citation

> US National Institutes of Health, RePORTER application 10626677, Axonal myelination of interneurons in cortex: functional significance and plasticity (2R56NS094499-06A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10626677. Licensed CC0.

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