# Activity-Dependent Mechanisms Regulating Synaptic Excitation and Inhibition in Neural Circuits

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $396,250

## Abstract

The ability of the cerebral cortex to perform incredibly complex functions resides in its intricate neural circuits
composed of a vast number of neurons. The synaptic interactions among cortical neurons ultimately manifest
as the interplay between excitation and inhibition, two opposing forces that work together to orchestrate the
spatiotemporal patterns of neuronal activity. Hence, the relationship between excitation and inhibition (E-I
relationship) is fundamental to many functional properties of cortical neurons such as the orientation selectivity
and contrast response function of visual cortical neurons. The importance of proper E-I relationship is also
underscored by the discovery of altered E-I relationship in many neurodevelopmental and psychiatric
disorders. However, the regulation of E-I relationship and the impacts of altering this relationship on the
functional response properties of cortical neurons remain poorly understood. Thus, the overall goal of this
project is to determine how the activity of individual neurons and homeostatic synaptic plasticity regulate
cortical excitation, inhibition, and E-I relationship. To this end, we used the developing mouse visual cortex as
a model system and developed molecular approaches to selectively reduce the excitability of a small number
of layer 2/3 pyramidal neurons in vivo, such that we can determine the cell-autonomous effect of neuronal
activity while minimizing the perturbation to the whole circuit. We found that these neurons counteract the
activity perturbation by homeostatic changes at a specific subset of excitatory and inhibitory synapses. These
results led to the central hypothesis that homeostatic plasticity differentially modifies distinct synaptic inputs of
individual cortical neurons to regulate their E-I relationship, thereby maintaining the activity levels and
functional response properties. We propose to combine molecular manipulations with optogenetic,
physiological, imaging, and anatomical methods to systematically delineate the homeostatic changes at
different synapses originating from distinct presynaptic neuronal types (Aim 1), to identify the underlying
synaptic mechanisms of input-specific homeostatic plasticity (Aim 2), and to determine the impact of these
synaptic changes on the visual response properties of neurons in vivo (Aim 3). The proposed research
connects three levels of investigations from synapse to circuit to system. The successful completion of this
project will provide insights into the role of homeostatic synaptic plasticity in regulating E-I relationship and
functional response properties of cortical neurons. The outcomes will also have an impact on our
understanding of how plasticity mechanisms help the brain cope with perturbations in general.

## Key facts

- **NIH application ID:** 9923747
- **Project number:** 5R01MH117089-03
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Mingshan Xue
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $396,250
- **Award type:** 5
- **Project period:** 2018-08-16 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9923747

## Citation

> US National Institutes of Health, RePORTER application 9923747, Activity-Dependent Mechanisms Regulating Synaptic Excitation and Inhibition in Neural Circuits (5R01MH117089-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9923747. Licensed CC0.

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