# Neural mechanism for the assembly of GABAergic circuits in the cerebral cortex

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $423,750

## Abstract

Project Summary (30 lines)
Experimental evidence supports the model that an imbalance in inhibitory and excitatory activity contributes to
many neurological disorders including epilepsy, schizophrenia, anxiety, autism spectrum disorders and
attention deficit/hyperactivity disorder. In the cerebral cortex, gamma-aminobutyric acid (GABA)ergic cortical
interneurons are the major source of inhibition and are known to be critical in maintaining activity balance in the
mature animal. However, the notion that developmental perturbations in GABAergic activity lead to defects in
the formation of cortical circuits with lasting structural and functional deficits that provide the substrate for
neurological illness, has not been explored in detail. The long-term goal of this research is to uncover how
early interneuron dysfunction in the developing pre and postnatal brain leads to lasting neurological
pathologies. The objective of this proposal is to reveal how extrinsic cues (nurture) and genetic programs
(nature) conspire to control interneuron circuit assembly during critical windows of perinatal development.
To this end, we will use the murine barrel cortex as a well-established model for the study of activity-dependent
circuit maturation and one that is inherently and robustly linked to the animal's extrinsic environment. Sensory
experience induces plasticity of sensory circuits in the cerebral cortex and is essential for sculpting neuronal
connectivity. However, the precise role of a diversity of specific interneuron subtypes in this process is
incompletely understood. We will focus our studies in cortical interneurons since our previous work indicates
that these neurons are exquisitely sensitive to environmental perturbations in the neonate. In the near term,
this proposal is aimed at revealing the identity interneurons subtypes that are activated by sensory cues (Aim
1). In addition, this project will assess how activity-dependent genetic programs regulate the emergence of
early connectivity (Aim 2). Finally, we wish to investigate the role of cortical interneurons in the formation of
sensory maps (Aim 3).
With respect to outcomes, our work is expected to identify neuronal types that regulate the emergence of
functional interneuron circuits. Given the accumulating experimental evidence implicating interneuron
dysfunction in brain disorders, understanding the mechanisms underlying activity-dependent plasticity for these
interneurons can provide invaluable insights for the development of therapeutic strategies

## Key facts

- **NIH application ID:** 9935962
- **Project number:** 5R01MH110553-05
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Natalia Vanesa De Marco Garcia
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $423,750
- **Award type:** 5
- **Project period:** 2016-08-01 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9935962

## Citation

> US National Institutes of Health, RePORTER application 9935962, Neural mechanism for the assembly of GABAergic circuits in the cerebral cortex (5R01MH110553-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9935962. Licensed CC0.

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