# Astrocytes modulate synaptic plasticity via Norepinephrine

> **NIH NIH K01** · CHILDREN'S RESEARCH INSTITUTE · 2020 · $218,629

## Abstract

Project Summary/Abstract
This proposal is for a K01 Mentored Career Development Award to Promote Faculty Diversity in Biomedical
Research for Dr. Nathan A. Smith, a new Assistant Professor of Pediatrics, and Pharmacology and Physiology
at Children’s National Health System (CNHS) and George Washington University School of Medicine and Health
Sciences (GWSMHS). Dr. Smith is establishing himself as a young investigator in mechanisms of synaptic
plasticity with a particular focus on the role of norepinephrine (NE) in astrocytic modulation of synaptic plasticity.
This K01 Award will provide Dr. Smith the support necessary to complete the following goals: (1) to acquire patch
clamping techniques for slice preparation; (2) to acquire and apply LTD protocols to slice preparation to
determine the role of astrocytes in learning and memory; (3) to acquire and learn advance pharmacology
techniques in order to specifically block a adrenergic receptors in astrocytes; (4) to develop the skills needed to
be an independent investigator through a variety of career development activities and mentorship. To achieve
these goals Dr. Smith has assembled a mentoring team comprised of a primary mentor, Dr. Vittorio Gallo, Chief
Research Officer at CNHS and a leading authority on glial signaling in health and disease, and two co-mentors:
Dr. Stefano Vicini, who has expertise in slice physiology and synaptic plasticity; and Dr. Jason Triplett, who has
expertise in sensory circuit development and function and one consultant/collaborator: Dr. Baljit Khakh (UCLA),
who is an established investigator and a leader in the field of glial biology and physiology.
NE is a major neurotransmitter that modulates a number of brain functions including synaptic plasticity. Recent
studies suggest that astrocytes could be involved in NE-induced network modulation. For example, NE has been
demonstrated to evoke global Ca2+ transients in cortical astrocytes. Additionally, NE has been shown to enhance
astrocytes ability to respond to local synaptic activity in the visual cortex. However, further investigation is needed
to elucidate the mechanisms of NE-mediated astrocytic effects on cortical networks and synaptic plasticity. To
that end, I will first explore if astrocytes are essential for NE-mediated LTD in the somatosensory cortex using
acute cortical slices in our novel GCaMP5G-tdTm/Aldh1l1 mice in Aim 1. In Aim 2, I will examine NE-induced
priming of astrocytes to respond to local synaptic activity. Specifically, I will explore NE-mediated enhancement
of astrocytic mGluR3-induced Ca2+ signaling to local synaptic activity in the somatosensory cortex, using both
acute cortical slices and in vivo preparations in GCaMP5G-tdTm/Aldh1l1 mice. Finally, in Aim 3, I will test the
hypothesis that astrocytes modulate NE-mediated cortical LTD via the release of ATP. Combined, the proposed
studies will provide novel insights into the role of astrocytes in synaptic regulation, and thereby in higher
inform...

## Key facts

- **NIH application ID:** 9896890
- **Project number:** 5K01NS110981-02
- **Recipient organization:** CHILDREN'S RESEARCH INSTITUTE
- **Principal Investigator:** Nathan A Smith
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $218,629
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9896890

## Citation

> US National Institutes of Health, RePORTER application 9896890, Astrocytes modulate synaptic plasticity via Norepinephrine (5K01NS110981-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9896890. Licensed CC0.

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