Altered hippocampal-prefrontal communication during anxiety-related avoidance in mice deficient for the autism-associated gene Pogz
- University of California, San Francisco, United States
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
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Altered hippocampal-prefrontal communication during anxiety-related avoidance in mice deficient for the autism-associated gene PogZDryad Digital Repository, doi:10.5061/dryad.Q6ZP44B9.
Article and author information
Author details
John LR Rubenstein
Vikaas Singh Sohal
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).
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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Altered hippocampal-prefrontal communication during anxiety-related avoidance in mice deficient for the autism-associated gene Pogz
eLife 9:e54835.
https://doi.org/10.7554/eLife.54835
