# TrkB.T1 signaling in astrocytes

> **NIH NIH R01** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2021 · $70,653

## Abstract

Astrocytes contribute to many facets of ‘normal’ central nervous system (CNS) physiology, including regulation
of neurotransmitters and K+ ions concentration, synaptic development, and synapse stabilization. These
functions are largely mediated at distal, fine, peripheral astrocyte processes (PAPs). It is at these processes that
astrocytes communicate with their neighbors, regulate ion and neurotransmitter levels and contribute to synapse
development and stabilization. Despite decades of research indicating astrocytes enwrap or contact excitatory
and inhibitory synaptic elements, with increased coverage of mature synapses, there is little known regarding
signals that recruit astrocyte PAPs to synaptic structures. RNA sequencing data we have generated (and
confirmed using multiple public resources) indicate astrocytes express very high levels of the BDNF receptor,
TrkB. Isoform specific identification demonstrates astrocytes predominately express the truncated form, TrkB.T1.
In cortex, TrkB.T1 is found almost exclusively in astrocytes. Global and astrocyte specific genetic deletion of
TrkB.T1 results in astrocytes with significantly reduced volume and branching complexities. Astrocytes lacking
TrkB.T1 show dysregulated expression of both perisynaptic genes associated with mature astrocyte function
and pro-synaptogenic genes. In vitro and in vivo we observed that TrkB.T1 KO astrocytes do not support normal
excitatory synaptogenesis or function as assessed by evaluation of pre and post synaptic excitatory elements
and neuronal mEPSC analysis. Preliminary in vitro data also indicate that TrkB.T1 KO astrocytes fail to enwrap
glutamatergic synapses, a phenotype we readily observe in WT astrocytes. In the current proposal we test the
hypothesis that BDNF signaling through the astrocytic TrkB.T1 receptor serves as a key signaling pathway in
recruiting astrocyte perisynaptic processes to glutamatergic synapses thus facilitating actin mediated structural
plasticity. In the current work we use ultrastructural imaging in WT and astrocyte specific TrkB.T1 KO mice to
determine if BDNF/TrkB.T1 signaling in astrocytes is necessary for astrocyte structural plasticity and function at
glutamatergic synapses (Aim 1). We evaluate the loss of astrocyte TrkB.T1 on neuronal synapse development
and function (Aim 2) and we use a combination of in vitro and in vivo approaches to identify the key signaling
mechanisms by which BDNF binding to astrocyte TrkB.T1 receptors engage downstream signaling mechanisms,
providing a molecular mechanistic framework linking astrocyte BDNF/TrkB.T1 signaling to actin cytoskeletal
reorganization, morphological refinement, process outgrowth and synapse enwrapment. These studies identify
a completely novel signaling pathway in astrocyte structural plasticity and have the potential to significantly
advance our understanding of astrocyte-synapse interactions. While disrupted BDNF/TrkB signaling is
implicated in many CNS disorders the relevance o...

## Key facts

- **NIH application ID:** 10347762
- **Project number:** 3R01NS120746-01S1
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Michelle L Olsen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $70,653
- **Award type:** 3
- **Project period:** 2021-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10347762

## Citation

> US National Institutes of Health, RePORTER application 10347762, TrkB.T1 signaling in astrocytes (3R01NS120746-01S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10347762. Licensed CC0.

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