# Linking Fast Timescale Neuron-Astrocyte Communication to Neural Circuit Function and Behavior

> **NIH NIH U19** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2023 · $446,812

## Abstract

Project Summary: Project 2 - Linking Fast Timescale Neuron-Astrocyte Communication to Neural
Circuit Function and Behavior
A fundamental yet unresolved question in neuroscience is how non-neuronal cells communicate with the
surrounding neurons, influence their function, and potentially affect animal behavior. Astrocytes are in a unique
position to modulate neural circuit function. They are ubiquitous in all CNS regions, express receptors for
neurotransmitters, neuromodulators, and neuropeptides, extend highly ramified processes that interact with
synapses and other CNS elements, and can operate as a syncytium partly due to their gap junctional coupling.
These structural and functional properties enable them to modulate synaptic plasticity and neuronal excitability.
Indeed, experimental evidence from multiple species and CNS regions now suggests that astrocytes modulate
neural circuit function and behavior on both slow and fast timescales. Nevertheless, precisely how astrocytes
respond to the composite molecular signals in their environment and how their intricate excitation patterns
influence neural circuit function on fast timescales (sub-seconds to minutes) remains unclear. This Project will
test the hypothesis that the heterogeneity of astrocyte transients can be understood by the temporal integration
of the time-varying molecular signals in their environment. Previous studies have also suggested that astrocytes
operate in at least two different modes: 1) Individually, and 2) as a syncytium. Yet, the relevance of these various
forms of chemical excitation for neural circuit function remains a mystery. This Project's second hypothesis is
that the different activity modes serve distinct physiological roles, enabling astrocytes to influence neural circuits
and behavior on different timescales. This Project proposes four major Aims to tackle these issues as part of a
team initiative. Aim 1 will determine how molecular signaling by local neurons relates to astrocyte excitation. Aim
2 focuses on elucidating how neuromodulator signaling by projection neurons influences astrocyte activity. Aim
3 will determine how targeted manipulation of astrocyte function (e.g., their ability to detect, temporally integrate,
communicate, or respond to extracellular signals) modulates their excitation patterns, neural circuit function, and
behavior. Aim 4 will generate a multilayer, multilevel atlas of the investigated neuron-astrocyte circuits. These
data will be acquired from a common set of mouse cortical regions involved in sensorimotor processing using a
reward-based quantitative behavioral assay. Computational analyses and modeling of this data will be used to
identify variables controlling astrocyte excitation, cell-intrinsic parameters constraining this activity, distinct
activity modes, and neuronal properties affected by these astrocytic features. Together, the functional and
anatomical studies of this Project will a) provide foundational information about ...

## Key facts

- **NIH application ID:** 10693171
- **Project number:** 5U19NS123719-03
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** Axel Nimmerjahn
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $446,812
- **Award type:** 5
- **Project period:** 2021-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10693171

## Citation

> US National Institutes of Health, RePORTER application 10693171, Linking Fast Timescale Neuron-Astrocyte Communication to Neural Circuit Function and Behavior (5U19NS123719-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10693171. Licensed CC0.

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