# Astrocyte regulation of amygdala circuit function

> **NIH NIH R56** · BAYLOR COLLEGE OF MEDICINE · 2024 · $608,297

## Abstract

Summary
Astrocytes are the most abundant type of glial cell in the brain, playing vital roles in all facets of brain physiology.
Given their central role in brain function, astrocytes have been implicated in a variety of psychiatric disorders
including autism, anxiety, schizophrenia, depression, and suicide. Despite the progress in understanding the
abnormalities in brain circuits and related molecular pathways, how astrocytes contribute to circuit dysfunction
associated with psychiatric disorders remains nascent. Recent studies have shown that astrocytes play an
essential role in amygdala function and associated behavioral outputs, which led us to further examine how
amygdala astrocytes contribute to human depression and associated suicide. Towards this, we performed
immunostaining from suicide decedents (N=20) and age-matched control, finding that the canonical astrocyte
marker GFAP and a key astrocyte transcription factor NFIA are both drastically increased in the amygdala of
suicide decedents. Recently, we reported that NFIA plays an essential role in the physiological activities of
astrocytes, neuronal circuit activity, and brain function in the adult hippocampus. This evidence led us to
hypothesize that astrocytic NFIA contributes to depression and associated suicide by regulating amygdala circuit
function. To determine whether astrocytic NFIA affects amygdala circuit function and associated depressive
behaviors, we utilized NFIA gain-of-function (GOF) and loss-of-function (LOF) mouse models. Preliminary
studies revealed that NFIA GOF induced depressive/anxiety behaviors, while NFIA LOF suppressed these
behaviors. In both cases, direct physiological analysis of amygdala circuit activity revealed significant and
complementary alterations.
 Therefore, based on the strength of these preliminary data, we propose the following specific aims. In
specific aim 1, we will determine the role of astrocytic NFIA in amygdala circuit activity and function using NFIA
GOF and LOF mice models. In specific aim 2, we will decipher how astrocytic NFIA regulates amygdala circuits
through GABA/MAOB. In this study, we will identify the target gene of NFIA using RNA-sequencing and
manipulate the target gene with pharmacological/genetic tools. In specific aim 3, we will delineate astrocytic
NFIA transcriptional networks in the amygdala. In this study, we will dissect the amygdala-specific NFIA
transcriptional networks and confirm this in human samples.

## Key facts

- **NIH application ID:** 10918318
- **Project number:** 5R56MH133822-02
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Junsung Woo
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $608,297
- **Award type:** 5
- **Project period:** 2023-09-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10918318

## Citation

> US National Institutes of Health, RePORTER application 10918318, Astrocyte regulation of amygdala circuit function (5R56MH133822-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10918318. Licensed CC0.

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