# Transcriptional Control of Gliogenesis in the CNS

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2022 · $400,125

## Abstract

Our studies on astrocyte diversity in the adult brain, revealed that NFIA is highly expressed in
adult astrocytes, across several brain regions. This led us to hypothesize that, in addition to its
pivotal role in astrocyte development, NFIA may also contribute to astrocyte function in the
adult. This hypothesis addresses a key “gap area” in our knowledge of astrocyte biology as the
transcriptional mechanisms that regulate adult astrocyte function are unknown.To ascertain
whether NFIA contributes to mature astrocyte function, we generated new transgenic mouse
lines that specifically eliminates it in adult astrocytes. Preliminary studies with these mice
revealed that astrocytes lacking NFIA exhibit region-specific changes in morphology, that are
coupled with impaired Ca2+ activity. These changes in astrocyte function directly impact
neuronal physiology, as synaptic activity is impaired and the induction of long term potentiation
(LTP) is inhibited. Accordingly, this inhibition of LTP corresponds with deficits in learning and
memory behaviors. Together, these observations reveal a novel transcriptional mechanism
regulating adult astrocyte function and associated neuronal circuits, while also defining a new
role for NFIA in the brain.
 Therefore, based on the strength of these preliminary data, we propose the following
specific aims. In specific aim 1, we will determine how loss of NFIA influences astrocyte
morphology and function across a diverse range of brain regions, over a series of timepoints,
post-deletion of NFIA. Functional studies will include assessing astrocyte membrane
conductance and calcium responses using genetically encoded GCaMP reporters. In specific
aim 2, we will focus on the hippocampus and determine how loss of NFIA in astrocytes
influences neuronal physiology, circuit function, and associated behaviors. These studies will
make use of basic physiological studies to assess basal and evoked/plasticity responses in
neurons. In specific aim 3, we have identified a set of candidate NFIA target genes that we will
functionally validate and in the second part of this aim will identify NFIA target gene networks in
astrocytes, across diverse brain regions to decode region specific vulnerabilities to NFIA loss in
the adult brain.

## Key facts

- **NIH application ID:** 10447125
- **Project number:** 5R01NS071153-13
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Benjamin Deneen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $400,125
- **Award type:** 5
- **Project period:** 2010-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447125

## Citation

> US National Institutes of Health, RePORTER application 10447125, Transcriptional Control of Gliogenesis in the CNS (5R01NS071153-13). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10447125. Licensed CC0.

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