Synaptic pruning in the female hippocampus is triggered at puberty by extrasynaptic GABAA receptors on dendritic spines

  1. Sonia Afroz
  2. Julie Parato
  3. Hui Shen
  4. Sheryl Sue Smith  Is a corresponding author
  1. University of California, Riverside, United States
  2. SUNY Downstate Medical Center, United States
  3. Tianjin Medical University, China

Abstract

Adolescent synaptic pruning is thought to enable optimal cognition because it is disrupted in certain neuropathologies, yet the initiator of this process is unknown. One factor not yet considered is the α4βδ GABAA receptor (GABAR), an extrasynaptic inhibitory receptor which first emerges on dendritic spines at puberty in female mice. Here we show that α4βδ GABARs trigger adolescent pruning. Spine density of CA1 hippocampal pyramidal cells decreased by half post-pubertally in female wild-type but not α4 KO mice. This effect was associated with decreased expression of kalirin-7 (Kal7), a spine protein which controls actin cytoskeleton remodeling. Kal7 decreased at puberty as a result of reduced NMDAR activation due to α4βδ-mediated inhibition. In the absence of this inhibition, Kal7 expression was unchanged at puberty. In the unpruned condition, spatial re-learning was impaired. These data suggest that pubertal pruning requires α4βδ GABARs. In their absence, pruning is prevented and cognition is not optimal.

Article and author information

Author details

  1. Sonia Afroz

    Department of Biomedical Sciences, University of California, Riverside, Riverside, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Julie Parato

    Department of Physiology and Pharmacology, SUNY Downstate Medical Center, Brooklyn, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Hui Shen

    School of Biomedical Engineering, Tianjin Medical University, Tianjin, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Sheryl Sue Smith

    Department of Physiology and Pharmacology, SUNY Downstate Medical Center, Brooklyn, United States
    For correspondence
    sheryl.smith@downstate.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 (#13-10374) of SUNY Downstate Medical Center (Animal Welfare Assurance Number: A3260-01). All perfusions were performed under urethane anesthesia, and every effort was made to minimize suffering.

Reviewing Editor

  1. Mary B Kennedy, California Institute of Technology, United States

Publication history

  1. Received: February 9, 2016
  2. Accepted: April 29, 2016
  3. Accepted Manuscript published: May 2, 2016 (version 1)
  4. Version of Record published: May 18, 2016 (version 2)

Copyright

© 2016, Afroz 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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  1. Sonia Afroz
  2. Julie Parato
  3. Hui Shen
  4. Sheryl Sue Smith
(2016)
Synaptic pruning in the female hippocampus is triggered at puberty by extrasynaptic GABAA receptors on dendritic spines
eLife 5:e15106.
https://doi.org/10.7554/eLife.15106

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