# Defining Astrocyte Heterogenity Across the Brainstem Respiratory Circuit

> **NIH NIH R21** · UNIVERSITY OF CONNECTICUT STORRS · 2020 · $201,250

## Abstract

PROJECT SUMMARY
Cortical astrocytes are genetically diverse; however, the physiological relevance of this is far from understood
because contributions of functionally discrete astrocyte subtypes to whole animal behavior is largely unknown.
The most compelling evidence supporting the possibility that astrocytes may have specialized physiological
roles is at the level of the brainstem where subsets of astrocytes contribute to the CO2/H+-dependent drive to
breathe (respiratory chemoreception) and inspiratory rhythm generation. Therefore, we will use the respiratory
circuit as a model system to identify unique genetic profiles of functionally defined subsets of astrocytes. We
will use RNA-seq to perform an unbiased evaluation of transcript expression in all cell types isolated from
chemosensitive regions, the inspiratory rhythm generating region and non-respiratory brainstem and cortical
regions. This analysis will focus on cell populations identified as astrocytes based on expression of cell type
specific markers. To correlate gene expression with function, we will use electrophysiological or Ca2+ imaging
techniques to functionally identify individual astrocytes in slices from each region for subsequent harvest and
targeted qPCR for genes expressed by each astrocyte subpopulation. The proposed work will enable
development of tools to study contributions of discrete subpopulations of astrocyte to respiratory behavior.
Also, since disruption of astrocyte CO2/H+ chemoreception contributes to disordered breathing in certain
diseases (e.g. Rett syndrome), the ability to selectively target CO2/H+-sensitive astrocytes would be an
attractive strategy for treating disordered breathing associated with this condition.

## Key facts

- **NIH application ID:** 10019601
- **Project number:** 5R21NS099887-02
- **Recipient organization:** UNIVERSITY OF CONNECTICUT STORRS
- **Principal Investigator:** Daniel K Mulkey
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $201,250
- **Award type:** 5
- **Project period:** 2019-09-18 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10019601

## Citation

> US National Institutes of Health, RePORTER application 10019601, Defining Astrocyte Heterogenity Across the Brainstem Respiratory Circuit (5R21NS099887-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10019601. Licensed CC0.

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