# The dual roles of GABA in excitatory synaptic plasticity

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2024 · $234,000

## Abstract

Project Summary
In the brain, neurons are connected by intermingled excitatory (E) and inhibitory (I) synapses. The correct E/I
balance is essential for proper brain function. Recent in vivo studies demonstrate that excitatory and inhibitory
synapses communicate with each other locally and inhibitory synapses could actively regulate the structure and
function of excitatory synapses. In vivo optogenetic stimulation and suppression of inhibitory activity decreases
and increases the stability of excitatory synapses, respectively. Our preliminary two-photon imaging and
chemogenetic data further show that PFC interneuron activity may affect excitatory synaptic plasticity throughout
brain development. These data strongly suggest that inhibitory synapses heterosynaptically regulate excitatory
synapses. However, there is much yet unknown about the cellular and synaptic mechanisms by which inhibitory
GABAergic synapses locally regulate excitatory glutamatergic synapse formation and elimination during brain
development. Using advanced optical techniques, this R21 grant proposal addresses key questions of
fundamental significance; 1) how do inhibitory synapses heterosynaptically regulate excitatory synapse structure
and function throughout brain development in an age-dependent manner? And 2) what signaling mechanisms
underlie the cross-talk between inhibitory and excitatory synapses during development and plasticity of neural
circuits? Our work will provide a powerful experimental framework for understanding how the brain achieves and
maintains E/I balance, and how this balance is altered in neurodevelopmental disorders arising from E/I
imbalance such as autism and schizophrenia.

## Key facts

- **NIH application ID:** 10948010
- **Project number:** 1R21MH137409-01
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Won Chan Oh
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $234,000
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10948010

## Citation

> US National Institutes of Health, RePORTER application 10948010, The dual roles of GABA in excitatory synaptic plasticity (1R21MH137409-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10948010. Licensed CC0.

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