1. Neuroscience
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Altered hippocampal-prefrontal communication during anxiety-related avoidance in mice deficient for the autism-associated gene Pogz

  1. Margaret M Cunniff
  2. Eirene Markenscoff-Papadimitriou
  3. Julia Ostrowski
  4. John LR Rubenstein
  5. Vikaas Singh Sohal  Is a corresponding author
  1. University of California, San Francisco, United States
Research Article
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Cite this article as: eLife 2020;9:e54835 doi: 10.7554/eLife.54835

Abstract

Many genes have been linked to autism. However, it remains unclear what long-term changes in neural circuitry result from disruptions in these genes, and how these circuit changes might contribute to abnormal behaviors. To address these questions, we studied behavior and physiology in mice heterozygous for Pogz, a high confidence autism gene. Pogz+/- mice exhibit reduced anxiety-related avoidance in the elevated plus maze (EPM). Theta-frequency communication between the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC) is known to be necessary for normal avoidance in the EPM. We found deficient theta-frequency synchronization between the vHPC and mPFC in vivo. When we examined vHPC-mPFC communication at higher resolution, vHPC input onto prefrontal GABAergic interneurons was specifically disrupted, whereas input onto pyramidal neurons remained intact. These findings illustrate how the loss of a high confidence autism gene can impair long-range communication by causing inhibitory circuit dysfunction within pathways important for specific behaviors.

Data availability

All data has been deposited in Dryad, DOI: doi:10.7272/Q6ZP44B9All code has been deposited in GitHub: https://github.com/mcunniff/PogZ_paper

The following data sets were generated

Article and author information

Author details

  1. Margaret M Cunniff

    Psychiatry, University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  2. Eirene Markenscoff-Papadimitriou

    Psychiatry, University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  3. Julia Ostrowski

    Psychiatry, University of California, San Francisco, San Francisco, United States
    Competing interests
    No competing interests declared.
  4. John LR Rubenstein

    Department of Psychiatry, University of California, San Francisco, San Francisco, United States
    Competing interests
    John LR Rubenstein, JLRR is cofounder, stockholder, and currently on the scientific board of Neurona, a company studying the potential therapeutic use of interneuron transplantation..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4414-7667
  5. Vikaas Singh Sohal

    Psychiatry, University of California, San Francisco, San Francisco, United States
    For correspondence
    vikaas.sohal@ucsf.edu
    Competing interests
    Vikaas Singh Sohal, VSS has received research funding from Neurona therapeutics and is on the scientific board of Empathic Therapeutics..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2238-4186

Funding

Simons Foundation (399853 and 514438)

  • Margaret M Cunniff
  • Eirene Markenscoff-Papadimitriou
  • Julia Ostrowski
  • John LR Rubenstein
  • Vikaas Singh Sohal

National Institute of Mental Health (R56MH117961 and R01MH117961)

  • Margaret M Cunniff
  • Vikaas Singh Sohal

Weill Insitute for Neurosciences

  • Vikaas Singh Sohal

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 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) protocols of the University of California, San Francisco (IACUC protocol #AN170116).

Reviewing Editor

  1. Laura L Colgin, University of Texas at Austin, United States

Publication history

  1. Received: January 2, 2020
  2. Accepted: November 5, 2020
  3. Accepted Manuscript published: November 6, 2020 (version 1)
  4. Version of Record published: November 23, 2020 (version 2)

Copyright

© 2020, Cunniff 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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