# Astrocytes modulate synaptic plasticity via Norepinephrine

> **NIH NIH K01** · UNIVERSITY OF ROCHESTER · 2021 · $218,628

## 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 Associate Professor of Neuroscience and
Associate Dean of Equity and Inclusion for research and research education. 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 with 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 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. Kerry O’Banion, Professor and Vice-Chair of Neuroscience, is a leading authority on glial
signaling in health and disease, and two co-mentors: Dr. Stefano Vicini (Georgetown), who has expertise in slice
physiology and synaptic plasticity; and Dr. Jason Triplett (Children’s National/George Washington), 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 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 ATP release. Combined, the proposed
studies will provide novel insights into the role of astrocytes in synaptic regulation and thereby in higher
information processing thro...

## Key facts

- **NIH application ID:** 10629844
- **Project number:** 7K01NS110981-04
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Nathan A Smith
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $218,628
- **Award type:** 7
- **Project period:** 2019-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10629844

## Citation

> US National Institutes of Health, RePORTER application 10629844, Astrocytes modulate synaptic plasticity via Norepinephrine (7K01NS110981-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10629844. Licensed CC0.

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