# Fundamental astrocyte biology in intact neural circuits

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $1,000,412

## Abstract

A central goal of neurobiology is to understand how the brain forms, stores, retrieves, modifies and
encodes information, and to determine how these operations go awry in neurological and psychiatric
diseases. The focus of this application is astrocytes, a type of glia. Long considered simply the brain's
glue, astrocytes are emerging as important regulators of neuronal function. Astrocytes are ubiquitous,
highly branched cells that tile the entire central nervous system, making contacts with neurons and blood
vessels, and serving diverse roles. Established roles include ion homeostasis, neurotransmitter
clearance, synapse formation/removal, synaptic modulation and contributions to neurovascular coupling.
Deciphering and exploiting the physiological roles of astrocytes in the brain is one of the major open
questions in neuroscience. This R35 application seeks to exploit technical and conceptual advances
made with R01, R21 and DP1 awards and combine them into a single nimble, long-term research
program to systematically explore and comprehensively understand the fundamental biology of
astrocytes within adult vertebrate intact neural circuits with the compass-driven goal of exploiting this
information for advancing new therapies. In this context, we define dysfunction as astrocyte process
withdrawal from synapses or altered astrocyte signaling, including trophic support, to synapses. Such
dysfunctions would alter established astrocyte roles including neurotransmitter clearance, synapse
regulation and maintenance. This in turn would alter the timing of synaptic transmission and microcircuit
function, contribute to excitotoxicity and perhaps trigger synapse removal. By exploiting novel
experimental tools and concepts generated as part of DP1 and R21 awards, and by applying them to the
exemplar striatal microcircuitry studied as part of successive R01 awards, we will determine how
astrocytes regulate intact neural microcircuits in vivo. We will test the overarching hypothesis that
astrocytes represent a hitherto largely overlooked mechanism in neural circuit function and in
neurological disorders. As part of these efforts, we will utilize, and if necessary develop, state-of-the-art
tools for molecular, cellular and circuit levels of evaluation. As described herein, our long-term
programmatic goal, therefore, is to deliver pivotal molecular, physiological and mechanistic insights on
astrocyte contributions to brain function and disease, laying the groundwork for therapeutic advances to
occur. We will continue to share openly our database resources and tools in order to enable additional
advances by others. In addition, the research program represents an outstanding opportunity and
laboratory environment for training the next generation of scientists and physician-scientists.

## Key facts

- **NIH application ID:** 10370362
- **Project number:** 5R35NS111583-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Baljit Khakh
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,000,412
- **Award type:** 5
- **Project period:** 2019-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10370362

## Citation

> US National Institutes of Health, RePORTER application 10370362, Fundamental astrocyte biology in intact neural circuits (5R35NS111583-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10370362. Licensed CC0.

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