# Role of GABAergic interneurons in developmental dysregulation of cortical function

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $418,210

## Abstract

Project Summary
 Neurodevelopmental disorders such as autism produce significant emotional,
physical, and economic consequences for affected individuals and their families. Autism
spectrum disorders (ASDs) affect approximately 1% of the worldwide population and are
associated with cognitive deficits in perception, social interaction, and communication, all
functions served by the cerebral cortex. While the cellular mechanisms underlying ASDs
remain unclear, recent evidence suggests disruption of GABAergic inhibitory
interneurons (INs) may contribute to abnormal development and function of cortical
circuits. Genetic studies of ASD patients have identified several candidate genes
including MeCP2, a gene strongly associated with Rett Syndrome (RTT), and IN-specific
deletion of MeCP2 produces many ASD-like phenotypes. However, little is known about
the specific cellular, synaptic, and circuit consequences of IN dysregulation. To address
this question, we propose to use a mouse model in which MeCP2 is deleted in a distinct
subpopulation of dendrite-targeting GABAergic INs, focusing on the mouse visual
system. Altered sensory processing is a hallmark of ASDs, and the wealth of knowledge
on the normal function of the visual cortex will provide critical context for interpreting the
cellular mechanisms underlying observed circuit and behavioral abnormalities.
Specifically, we will test the following three hypotheses: (1) MeCP2 expression in
somatostatin-expressing (SOM) INs regulates cortical neuronal morphology and
connectivity. (2) SOM-IN dysregulation contributes to cortical circuit dysfunction in the
MeCP2 model. (3) SOM-IN-specific MeCP2 deletion impairs visual perception. We will
combine electrophysiological and anatomical analyses ex vivo with high-density
neuronal recordings and behavioral analyses in vivo. This approach will allow us to
generate novel insights into the links between structural and synaptic dysregulation and
dysfunction of neural circuits in an established model of neurodevelopmental disorders.

## Key facts

- **NIH application ID:** 10169518
- **Project number:** 5R01MH113852-05
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** JESSICA A CARDIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $418,210
- **Award type:** 5
- **Project period:** 2017-08-03 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10169518

## Citation

> US National Institutes of Health, RePORTER application 10169518, Role of GABAergic interneurons in developmental dysregulation of cortical function (5R01MH113852-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10169518. Licensed CC0.

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