Sex differences in cerebellar synaptic transmission and sex-specific responses to autism-linked Gabrb3 mutations in mice

Abstract

Neurons of the cerebellar nuclei (CbN) transmit cerebellar signals to premotor areas. The cerebellum expresses several autism-linked genes, including Gabrb3, which encodes GABAA receptor β3 subunits and is among the maternal alleles deleted in Angelman syndrome. We tested how this Gabrb3 m-/p+ mutation affects CbN physiology in mice, separating responses of males and females. Wild-type mice showed sex differences in synaptic excitation, inhibition, and intrinsic properties. Relative to females, CbN cells of males had smaller synaptically evoked mGluR1/5-dependent currents, slower Purkinje-mediated IPSCs, and lower spontaneous firing rates, but rotarod performances were indistinguishable. In mutant CbN cells, IPSC kinetics were unchanged, but mutant males, unlike females, showed enlarged mGluR1/5 responses and accelerated spontaneous firing. These changes appear compensatory, since mutant males but not females performed indistinguishably from wild-type siblings on the rotarod task. Thus, sex differences in cerebellar physiology produce similar behavioral output, but provide distinct baselines for responses to mutations.

Article and author information

Author details

  1. Audrey A Mercer

    Northwestern University Interdepartmental Neuroscience Program, Northwestern University, Evanston, United States
    Competing interests
    No competing interests declared.
  2. Kristin J Palarz

    Department of Neurbiology, Northwestern University, Evanston, United States
    Competing interests
    No competing interests declared.
  3. Nino Tabatadze

    Department of Neurobiology, Northwestern University, Evanston, United States
    Competing interests
    No competing interests declared.
  4. Catherine S Woolley

    Department of Neurobiology, Northwestern University, Evanston, United States
    Competing interests
    No competing interests declared.
  5. Indira M Raman

    Department of Neurobiology, Northwestern University, Evanston, United States
    For correspondence
    i-raman@northwestern.edu
    Competing interests
    Indira M Raman, Reviewing editor, eLife.

Reviewing Editor

  1. Michael Häusser, University College London, United Kingdom

Ethics

Animal experimentation: All procedures conformed to institutional guidelines and were approved by the Institutional Animal Care and Use Committee of Northwestern University (Animal Welfare Assurance Number, A3283-01; IACUC Study #IS00000242).

Version history

  1. Received: March 19, 2015
  2. Accepted: April 13, 2016
  3. Accepted Manuscript published: April 14, 2016 (version 1)
  4. Version of Record published: May 24, 2016 (version 2)
  5. Version of Record updated: June 17, 2016 (version 3)

Copyright

© 2016, Mercer 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. Audrey A Mercer
  2. Kristin J Palarz
  3. Nino Tabatadze
  4. Catherine S Woolley
  5. Indira M Raman
(2016)
Sex differences in cerebellar synaptic transmission and sex-specific responses to autism-linked Gabrb3 mutations in mice
eLife 5:e07596.
https://doi.org/10.7554/eLife.07596

Share this article

https://doi.org/10.7554/eLife.07596

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