# Linking Neuron-Astrocyte Communication to Long-Term Changes in Neural Circuit Function and Behavior

> **NIH NIH U19** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2023 · $437,274

## Abstract

Project Summary: Project 3- Linking Neuron-Astrocyte Communication to Long-Term
Changes in Neural Circuit Function and Behavior
Astrocytes, which are often dubbed as the passive support cells, in fact closely associate with a vast number
of neuronal synapses and sense their activity, making them ideal cellular detectors and integrators of
synaptic transmission. Moreover, astrocytes remodel synaptic circuitry and function by instructing synapse
formation and plasticity. However, whether and how astrocytes play an instructive role to mediate
complex behaviors remains unknown.
The overarching hypothesis to be tested in this collaborative project is that astrocytes act as temporal
integrators, which detect and integrate local synaptic activity and long-projecting neuromodulatory
transmissions. In this subproject (Project 3), the specific hypothesis to be tested is that signal
integration property of individual or syncytia of astrocytes allows them to become entrained by
experience-driven synaptic activity during acquisition of goal-directed behaviors. These entrained astrocytes
become “engaged” with the learned behavior by epigenetic remodeling of astrocytic chromatin, leading to
long-term changes in astrocytic gene expression, structure and function (Aim1). This engagement
allows the astrocytes to rewire the local synaptic circuitry in two ways; 1) by changing the numbers of
excitatory and/or inhibitory synapses within their domains, thus modulate the local excitation/inhibition
balance, and 2) by altering their synapse association and neuropil infiltration, thus controlling
extracellular concentrations of neurotransmitters. Preliminary findings suggest that astrocyte-
mediated synaptic remodeling is not necessary for learning, but rather for the adaptability of the
learned behaviors. These findings point out a specific role for these proposed behaviorally-engaged
astrocytes in rewiring of the underlying circuits to prepare these circuits for a future eventuality, in
which the learned behavior is no longer effective -e.g. the effort to achieve the desired outcome exceeds
the value of the reward (Aim2). These behaviorally-engaged astrocytes form ensembles with their
neuronal counter parts, both of which can be identified by immediate early gene expression. During the
performance of behaviors, these astrocyte-neuron ensembles are primed to sense the changes in action/
outcome contingency so that they can instruct to stop the learned behaviors (Aim3).
Working in concert with other teams, these hypotheses will be tested in three aims, and a mechanistic blueprint
for astrocyte-neuron communication in the awake behaving mouse brain will be generated. Therefore,
these proposed studies are poised to reveal how astrocytes respond to, integrate, and modulate
neuronal connectivity in long-time scales. Furthermore, in conjunction with other teams, these findings
will guide the development of novel genetically encoded indicators and viral tools to interrogate ne...

## Key facts

- **NIH application ID:** 10693174
- **Project number:** 5U19NS123719-03
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** Cagla Eroglu
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $437,274
- **Award type:** 5
- **Project period:** 2021-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10693174

## Citation

> US National Institutes of Health, RePORTER application 10693174, Linking Neuron-Astrocyte Communication to Long-Term Changes in Neural Circuit Function and Behavior (5U19NS123719-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10693174. Licensed CC0.

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