# Astrocyte transcriptional responses to neuronal activity in the olfactory bulb

> **NIH NIH K99** · BAYLOR COLLEGE OF MEDICINE · 2022 · $99,098

## Abstract

Project Summary/Abstract
 Astrocytes are non-neuronal cells widely distributed in the brain and astrocyte-neuron communication
play critical roles in modulation of behavior. Sensory stimuli like chemical signals of odors activate neurons to
induce gene expression changes that facilitate sensory processing. While these are well understood in
neurons, whether similar transcriptomic changes also occur in astrocytes are unknown. Here, using in vivo
chemogenetic models of neuronal activation, we show astrocytes indeed undergo robust gene expression
changes after neuronal activation. A screen through these changes identified a neuromodulator transporter
Slc22a3 in olfactory bulb astrocytes. Since preliminary studies revealed odor-evoked neuronal activation also
increased astrocytic Slc22a3 in the olfactory bulb, we first asked how Slc22a3 affect astrocyte function in the
olfactory bulb? We show that overexpression of astrocyte-specific Slc22a3 led to increased sensitivity to odors
implying that astrocytic Slc22a3 affects astrocyte-neuron communication. This leads to the hypothesis that
transcriptional activation of astrocytic Slc22a3 is essential for mediating astrocyte-neuron communication
during olfactory processing. To test this hypothesis, we propose to use Slc22a3 gain-of-function and loss-of-
function mouse models to investigate how astrocytic Slc22a3 affect behaviors and cellular properties of
astrocytes (Aim1). Since Slc22a3 transports neuromodulators like serotonin, we next asked how Slc22a3-
mediated serotonin transport affect molecular properties of olfactory bulb astrocytes? Since recent studies
have shown that serotonin can be directly incorporated into histones to activate transcription, we focused on
this epigenetic modification of histone serotonoylation. We show that in olfactory bulb astrocytes,
overexpression of Slc22a3 controls histone serotonoylation levels. Therefore, we propose to genetically
manipulate astrocytic Slc22a3 expression to determine Slc22a3-mediated histone serotonoylation dynamics in
the olfactory bulb (Aim2). Furthermore, preliminary data also revealed that histone serotonoylation levels are
increased in astrocytes after odor-evoked neuronal activation. Therefore, using experimental approaches
established in Aims1-2, I will directly investigate the function of astrocytic histone serotonoylation in the
olfactory bulb (Aim3). Taken together, these results will reveal genetic and epigenetic mechanisms of how
astrocytes contribute to olfactory processing. For my career development these studies will provide training in
olfactory bulb biology under my mentor Dr. Deneen (expert in astrocyte biology) and co-mentor Dr. Arenkiel
(expert in olfactory bulb circuits and behaviors) at Baylor College of Medicine. Since astrocytes are intimately
connected with neurons and are dysregulated in all neurological disorders, the broader goal of this proposal is
to uncover how astrocytes contribute to healthy processing of the chemical ...

## Key facts

- **NIH application ID:** 10448625
- **Project number:** 1K99DC019668-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Debosmita Sardar
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $99,098
- **Award type:** 1
- **Project period:** 2022-03-10 → 2024-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448625

## Citation

> US National Institutes of Health, RePORTER application 10448625, Astrocyte transcriptional responses to neuronal activity in the olfactory bulb (1K99DC019668-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10448625. Licensed CC0.

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