# Novel Genetically Encoded Indicators for Interrogating Neuron-Astrocyte Communication Across Timescales

> **NIH NIH U19** · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 2023 · $422,793

## Abstract

Project Summary: Project 4 - Novel Genetically Encoded Indicators for Interrogating Neuron-Astrocyte
Communication Across Timescales
Astrocytes, the most abundant cell type in the brain, have long thought to be primarily passive support cells.
Considerable evidence from the labs has shown that astrocyte-synapse displays a dynamic and bi-directional
relationship, with local synaptic transmission and neuromodulation being capable of shaping astrocytic activity
and PAP structural plasticity, and astrocyte shaping synapse formation and modulating plasticity and signaling
via secreted factors and adhesion molecules. These critical advances in understanding astrocyte biology in
vivo are primarily due to recent applications of modern techniques initially designed for studying neurons to
direct manipulation and interrogation of astrocytes. Though the concept of astrocytes as integral and
modulatory components of neural circuit is emerging, a mechanistic understanding of causative and correlative
roles of astrocytes in operating neural circuit and contribution to the complex behaviors is still lacking, which
necessities and drives the development of improved tools. Thus, a large-scale protein engineering effort to
develop an improved tool to address unsolved questions to achieve a mechanistic understanding of causal and
correlative roles of astrocyte in neuronal circuit function and contributions to behavior is being proposed.
Provided items include:
 1. a set of optimized red-shifted glutamate, GABA, DA, and NE sensors,
 2. a set of green and red-shifted synaptic glutamate/GABA sensors to probe neuron-astrocyte connectivity
 and extracellular NT transients at tripartite synapses, and
 3. interrogate cross-talk between PKA and calcium in astrocytes and optimized green and red-shifted
 kinases sensors for in vivo applications.
These new sensors will be applied to study 1) how experience-dependent changes that drive complex patterns
of neurotransmitter or neuromodulatory signaling lead to the changes in astrocytic activity and 2) how
astrocytes modulate synaptic activity via structural plasticity across various temporal scales. The contribution is
significant because these improved tools will permit new hypotheses being tested in astrocyte biology. This
toolset will provide needed tools to facilitate experiments proposed here and provide a rich resource to the field
to bring full swing the investigation of astrocyte-neuron interaction underlying complex behavioral and cognitive
processes that are inaccessible via currently existing approaches.

## Key facts

- **NIH application ID:** 10693178
- **Project number:** 5U19NS123719-03
- **Recipient organization:** SALK INSTITUTE FOR BIOLOGICAL STUDIES
- **Principal Investigator:** Lin Tian
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $422,793
- **Award type:** 5
- **Project period:** 2021-08-15 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10693178

## Citation

> US National Institutes of Health, RePORTER application 10693178, Novel Genetically Encoded Indicators for Interrogating Neuron-Astrocyte Communication Across Timescales (5U19NS123719-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10693178. Licensed CC0.

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