# The role of astrocyte-neuron signaling in closing a critical period required for motor circuit structure function and behavior

> **NIH NIH R00** · WASHINGTON UNIVERSITY · 2024 · $109,310

## Abstract

PROJECT SUMMARY
Significance: Neural circuit assembly requires activity-dependent refinement of circuit architecture (e.g.
plasticity) to produce stereotyped behavior. Neurons are particularly susceptible to functional and structural
plasticity during early developmental windows called critical periods. Failure to terminate critical period plasticity
adversely affects mature circuit function in both animal models and humans (e.g. autism and epilepsy), yet the
mechanisms that close critical periods are largely unknown. This Pathway to Independence Award proposal
seeks to define conserved cellular and molecular mechanisms that promote critical period closure, and to
understand how critical periods shape circuit architecture to ensure proper locomotor behavior.
Project Goals: We will leverage the unique strengths of two model systems- Drosophila and zebrafish- to define
the cellular and molecular mechanisms that instruct neural plasticity. Specifically, we will determine how
astrocyte-neuron signaling governs critical period timing, and how changes in critical period timing influence
long-term circuit structure and function. First, we will test how microtubule stability influences motor dendrite
structure to test how structural plasticity is executed (Aim 1). Then, we will test how critical period plasticity
influences motor circuit maintenance to determine why structural plasticity is temporally restricted (Aim 2).
Finally, we will use zebrafish to determine how astrocytes regulate plasticity in distinct neural circuits with
different patterns of plasticity (Aim 3).
Candidate and environment: Dr. Ackerman was trained in molecular genetics and developmental neuroscience
in the laboratory of Dr. Kelly Monk at WashU School of Medicine, where she used forward and reverse genetic
strategies to uncover regulators of myelination (NS087801). She then joined the laboratory of the renowned
neurobiologist Dr. Chris Doe (UO, HHMI/NAS). There, she defined a novel critical period of plasticity in the
developing Drosophila motor circuit and uncovered a series of astrocyte-derived molecular regulators of critical
period closure (NS098690). Dr. Ackerman has chosen to open her laboratory within the Center for Brain
Immunology and Glia at WashU (Department of Pathology and Immunology). The Center brings together faculty
and physicians across multiple departments to understand how non-neuronal cells shape nervous system
development, function, and disease. With the support of the Center and pre-existing mentors at WashU (Dr. Jim
Skeath, Dr. Lila Solnica-Krezel, Dr. Aaron Diantonio, and others), she and her team are well-equipped to uncover
how neuron-glia interactions regulate developmental plasticity.

## Key facts

- **NIH application ID:** 10987696
- **Project number:** 3R00NS121137-04S1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Sarah D Ackerman
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $109,310
- **Award type:** 3
- **Project period:** 2021-04-15 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10987696

## Citation

> US National Institutes of Health, RePORTER application 10987696, The role of astrocyte-neuron signaling in closing a critical period required for motor circuit structure function and behavior (3R00NS121137-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10987696. Licensed CC0.

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