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Astrocytes refine cortical connectivity at dendritic spines

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Cite as: eLife 2014;3:e04047 doi: 10.7554/eLife.04047

Abstract

During cortical synaptic development, thalamic axons must establish synaptic connections despite the presence of the more abundant intracortical projections. How thalamocortical synapses are formed and maintained in this competitive environment is unknown. Here, we show that astrocyte-secreted protein hevin is required for normal thalamocortical synaptic connectivity in the mouse cortex. Absence of hevin results in a profound, long-lasting reduction in thalamocortical synapses accompanied by a transient increase in intracortical excitatory connections. Three-dimensional reconstructions of cortical neurons from serial section electron microscopy (ssEM) revealed that, during early postnatal development, dendritic spines often receive multiple excitatory inputs. Immuno-EM and confocal analyses revealed that majority of the spines with multiple excitatory contacts (SMECs) receive simultaneous thalamic and cortical inputs. Proportion of SMECs diminishes as the brain develops, but SMECs remain abundant in Hevin-null mice. These findings reveal that, through secretion of hevin, astrocytes control an important developmental synaptic refinement process at dendritic spines.

Article and author information

Author details

  1. W Christopher Risher

    1. Department of Cell Biology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Sagar Patel

    1. Department of Cell Biology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Il Hwan Kim

    1. Department of Cell Biology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Akiyoshi Uezu

    1. Department of Cell Biology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Srishti Bhagat

    1. Department of Neurobiology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Daniel K Wilton

    1. Department of Neurology, FM Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Louis-Jan Pilaz

    1. Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Jonnathan Singh Alvarado

    1. Department of Cell Biology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Osman Y Calhan

    1. Department of Cell Biology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Debra L Silver

    1. Department of Cell Biology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Beth Stevens

    1. Department of Neurology, FM Kirby Neurobiology Center, Boston Children's Hospital, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Nicole Calakos

    1. Department of Neurobiology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Scott H Soderling

    1. Department of Cell Biology, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Cagla Eroglu

    1. Department of Cell Biology, Duke University Medical Center, Durham, United States
    For correspondence
    1. c.eroglu@cellbio.duke.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocol (# A195-11-08) of Duke University Medical Center. The mice were euthanized by following the approved protocols which were performed under avertin anesthesia, and every effort was made to minimize suffering.

Reviewing Editor

  1. Liqun Luo, Reviewing Editor, Howard Hughes Medical Institute, Stanford University, United States

Publication history

  1. Received: July 16, 2014
  2. Accepted: December 16, 2014
  3. Accepted Manuscript published: December 17, 2014 (version 1)
  4. Version of Record published: January 8, 2015 (version 2)

Copyright

© 2014, Risher 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.

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