# Control of Astrocyte Development and Astrocyte-Synapse Interactions

> **NIH NIH R01** · DUKE UNIVERSITY · 2021 · $422,687

## Abstract

Astrocytes are highly complex cells with hundreds of thousands of fine processes that contact and
ensheathe neuronal synapses. These perisynaptic astrocyte processes actively participate in synaptic
development and function by regulating neurotransmitter release, maintaining ion homeostasis, and
modulating synaptic connectivity. Despite the importance of astrocytes in synaptic development and function,
we know very little about the molecular and cellular mechanisms that control the establishment of complex
astrocyte morphology and astrocyte-synapse interactions.
 In our preliminary experiments, we found that in the mouse visual cortex the establishment of the
complex astrocyte morphology is a developmentally regulated process that occurs during a period of
extensive synapse formation. Manipulation of visual experience, i.e. dark rearing mice during first three
weeks of postnatal development, strongly stunts cortical astrocyte development, indicating that experience-
dependent changes in synaptic connectivity can alter morphological maturation of astrocytes. How is the
complex astrocyte morphology attained and remodeled? To mechanistically address this question, we
developed a primary cortical neuron and astrocyte co-culture system that takes advantage of the following
basic observation: Astrocytes cultured by themselves have a simple fibroblast-like morphology; however,
contact with neurons, even for a short period of time, is sufficient to trigger extensive elaboration of the
astrocytes. This morphological shift in astrocytes is primarily driven by direct neuronal contact, but not by
soluble secreted factors. Using this system, we conducted a candidate-based genetic screen and identified
that the astrocytic expression of neuroligin (NL) family cell-adhesion molecules (CAMs), NL1, NL2 and NL3
control neuronal adherence and morphological maturation of astrocytes in vitro and in vivo. Based on these
findings, our objective here is to determine the functions of NLs in astrocyte development and astrocyte-
synapse interactions. To do so, we will test three hypotheses: 1) Astrocytic NLs control astrocyte
morphological complexity by mediating astrocyte-synapse association. 2) NLs perform these functions via
their extracellular interactions with axonal/presynaptic neurexins and 3) via their critical intracellular domains
that control cytoskeletal dynamics within astrocytes.
 These studies have the potential to significantly advance our understanding of the molecular basis of
astrocyte development and astrocyte-synapse interactions. Moreover, the results obtained here will provide
critical new avenues for studying the formation of the tripartite synapses and reveal a new paradigm through
which astrocytic NLs control brain development, a process that may be critically impaired in neurological
disorders.!

## Key facts

- **NIH application ID:** 10142549
- **Project number:** 5R01NS102237-04
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Cagla Eroglu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $422,687
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10142549

## Citation

> US National Institutes of Health, RePORTER application 10142549, Control of Astrocyte Development and Astrocyte-Synapse Interactions (5R01NS102237-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10142549. Licensed CC0.

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