# Integrating Astrocytes into Models of Neural Circuits Regulating Behavior

> **NIH NIH U19** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2021 · $431,748

## Abstract

Project Summary: Project 1 - Integrating Astrocytes into Models of Neural Circuits Regulating Behavior
Astrocytes, the most abundant cells in the brain, express various receptors of neurotransmitters and
neuromodulators and extend thousands of fine cellular leaflets, wrapping around the pre- and postsynaptic
neuronal elements. Studies over past decades have portrayed a picture where astrocytes actively respond to
both local and long projecting neuronal activities, first increasing cytosolic calcium ions (Ca2+) or other internal
signals, then influencing the concentration of extracellular factors and ions and ultimately modifying its gene
expression pattern and morphology. Thus, while neurons are unarguably a necessary player in neural circuits,
astrocytes need to be accounted and integrated into the neural circuits to achieve a more complete
understanding on how the brain works or dysfunctions. Indeed, it is appealing to consider astrocytes and
neurons as a unified circuit, since they participate in the brain information processing in complementary
manners in terms of both temporal and spatial domains. However, precisely how astrocytes temporally
and spatially integrate the molecular signals from diverse neuronal signals, particularly during behavior,
remains poorly understood. Likewise, how the diversity of astrocyte activity, in turn, influences neural circuit
function on various timescales, is unclear. The hypothesis is that a deeper and more complete understanding
on the astrocytes’ contribution to neural circuits can be achieved by systematically measuring,
manipulating, quantifying and modeling the astrocytes’ functional and structural status in the context of
controllable and quantifiable behavior tasks, which is the collective effort proposed by this U19 team.
Leveraging the improved and comprehensive measurement and manipulation of (a) various
neurotransmitters and neuromodulators, (b) multi-scale and multi-level anatomical information, (c)
important intracellular messengers, and (d) genomic signals from the efforts in the other three projects, this
project focuses on building mathematical models (Aim 1) to quantitatively interpret and predict how astrocytes
integrate various neuronal signals, and how the astrocytes regulate the neural circuit in both fast-time and
long-term scales. Considering that astrocytes have complex spatiotemporal dynamics and their morphologies
are irregular and in close contact with diverse neurons, one needs to accurately quantify the astrocyte
dynamics (Aim 2) and faithfully reconstruct the anatomy (Aim 3), to provide the necessary quantitative
description of observations and the fundamental geometric constraints to the model development.
Reciprocally, this project will identify knowledge gaps to suggest new experiments, make predictions to
generate new hypothesis and provide quantification tools to facilitate scientific discoveries for the other three
projects and more broadly for the neuroscience community.

## Key facts

- **NIH application ID:** 10294803
- **Project number:** 1U19NS123719-01
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** Guoqiang Yu
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $431,748
- **Award type:** 1
- **Project period:** 2021-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10294803

## Citation

> US National Institutes of Health, RePORTER application 10294803, Integrating Astrocytes into Models of Neural Circuits Regulating Behavior (1U19NS123719-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10294803. Licensed CC0.

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