# Activity-dependent regulation of Sonic hedgehog signaling incortical astrocytes

> **NIH NIH R21** · DREXEL UNIVERSITY · 2022 · $227,250

## Abstract

PROJECT ABSTRACT
Understanding the mechanisms by which the CNS adapts to novel experiences and changing
environments is a fundamental goal of neuroscience. Following experience and neural activity,
neurons undergo changes in gene expression and synaptic organization that facilitate such
adaptation. Though historically regarded as simple support cells for neurons, astrocytes are
gaining increasing recognition as essential elements of the synapse, modulating synaptic
connectivity and function. This suggests that reciprocal interactions between neurons and
astrocytes are likely to be involved in experience-dependent synaptic plasticity. The molecular
mechanisms underlying neuronal interactions with astrocytes during experience-dependent
activity are not well understood. In previous studies, we identified astrocytes as the predominant
cell type transducing Sonic hedgehog (Shh) signaling derived from neurons in the postnatal and
adult cortex. Selective disruption of Shh activity in astrocytes impairs structural and functional
properties of cortical neurons, demonstrating that Shh signaling is required for the proper
establishment of developing circuits. In this study, we propose to examine the role of activity in
regulating Shh signaling. We will use an enriched environment with complex stimuli that include
novelty, increased physical activity and social interactions, to investigate the role of experience
in stimulating Shh. In Aim 1, we will identify the stimuli that promote experience-dependent Shh
activity and determine whether it is modality-specific. In Aim 2, we will use genetic marking
strategies and chemogenetic approaches to identify the cells that initiate experience-dependent
Shh signaling and determine whether neuronal activity stimulates Shh activity. These data will
lay the foundation for further mechanistic studies aimed at elucidating the molecular programs
initiated by activity-dependent neuron-astrocyte communication mediated by Shh signaling.

## Key facts

- **NIH application ID:** 10320950
- **Project number:** 5R21NS116664-02
- **Recipient organization:** DREXEL UNIVERSITY
- **Principal Investigator:** Anna Denise Resurreccion Garcia
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $227,250
- **Award type:** 5
- **Project period:** 2021-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10320950

## Citation

> US National Institutes of Health, RePORTER application 10320950, Activity-dependent regulation of Sonic hedgehog signaling incortical astrocytes (5R21NS116664-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10320950. Licensed CC0.

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