1. Neuroscience
Download icon

Astrocyte morphogenesis is dependent on BDNF signaling via astrocytic TrkB.T1

  1. Leanne M Holt
  2. Raymundo D Hernandez
  3. Natasha L Pacheco
  4. Beatriz Torres Ceja
  5. Muhannah Hossain
  6. Michelle Olsen  Is a corresponding author
  1. University of Alabama at Birmingham, United States
  2. Virginia Polytechnic Institute and State University, United States
Research Article
  • Cited 21
  • Views 2,931
  • Annotations
Cite this article as: eLife 2019;8:e44667 doi: 10.7554/eLife.44667
Voice your concerns about research culture and research communication: Have your say in our 7th annual survey.

Abstract

Brain derived neurotrophic factor (BDNF) is a critical growth factor involved in the maturation of the CNS, including neuronal morphology and synapse refinement. Herein, we demonstrate astrocytes express high levels of BDNF's receptor, TrkB (in the top 20 of protein-coding transcripts), with nearly exclusive expression of the truncated isoform, TrkB.T1, which peaks in expression during astrocyte morphological maturation. Using a novel culture paradigm, we show that astrocyte morphological complexity is increased in the presence of BDNF and is dependent upon BDNF/TrkB.T1 signaling. Deletion of TrkB.T1, globally and astrocyte-specifically, in mice revealed morphologically immature astrocytes with significantly reduced volume, as well as dysregulated expression of perisynaptic genes associated with mature astrocyte function. Indicating a role for functional astrocyte maturation via BDNF/TrkB.T1 signaling, TrkB.T1 KO astrocytes do not support normal excitatory synaptogenesis or function. These data suggest a significant role for BDNF/TrkB.T1 signaling in astrocyte morphological maturation, a critical process for CNS development.

Data availability

Sequencing data have been deposited in GEO under accession code GSE122176.

The following data sets were generated

Article and author information

Author details

  1. Leanne M Holt

    Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Raymundo D Hernandez

    School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Natasha L Pacheco

    Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9617-8887
  4. Beatriz Torres Ceja

    School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Muhannah Hossain

    School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Michelle Olsen

    School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, United States
    For correspondence
    molsen1@vt.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1394-664X

Funding

National Institute of Neurological Disorders and Stroke (F31NS100259)

  • Leanne M Holt

National Institute of Neurological Disorders and Stroke (R01NS075062)

  • Michelle Olsen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experiments were performed according to NIH guidelines and with approval from the Animal Care and Use Committee of the University of Alabama at Birmingham (#20650) and Virginia Polytechnic Institute and State University (#17-012). Every effort was made to minimize pain and discomfort.

Reviewing Editor

  1. Cagla Eroglu, Duke University, United States

Publication history

  1. Received: December 22, 2018
  2. Accepted: August 20, 2019
  3. Accepted Manuscript published: August 21, 2019 (version 1)
  4. Version of Record published: September 4, 2019 (version 2)
  5. Version of Record updated: March 19, 2021 (version 3)

Copyright

© 2019, Holt et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,931
    Page views
  • 477
    Downloads
  • 21
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Neuroscience
    Eun Ju Shin et al.
    Research Article Updated

    Studies in rats, monkeys, and humans have found action-value signals in multiple regions of the brain. These findings suggest that action-value signals encoded in these brain structures bias choices toward higher expected rewards. However, previous estimates of action-value signals might have been inflated by serial correlations in neural activity and also by activity related to other decision variables. Here, we applied several statistical tests based on permutation and surrogate data to analyze neural activity recorded from the striatum, frontal cortex, and hippocampus. The results show that previously identified action-value signals in these brain areas cannot be entirely accounted for by concurrent serial correlations in neural activity and action value. We also found that neural activity related to action value is intermixed with signals related to other decision variables. Our findings provide strong evidence for broadly distributed neural signals related to action value throughout the brain.

    1. Neuroscience
    Gonçalo Lopes et al.
    Research Article Updated

    Real-time rendering of closed-loop visual environments is important for next-generation understanding of brain function and behaviour, but is often prohibitively difficult for non-experts to implement and is limited to few laboratories worldwide. We developed BonVision as an easy-to-use open-source software for the display of virtual or augmented reality, as well as standard visual stimuli. BonVision has been tested on humans and mice, and is capable of supporting new experimental designs in other animal models of vision. As the architecture is based on the open-source Bonsai graphical programming language, BonVision benefits from native integration with experimental hardware. BonVision therefore enables easy implementation of closed-loop experiments, including real-time interaction with deep neural networks, and communication with behavioural and physiological measurement and manipulation devices.