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Daily oscillation of the excitation/inhibition ratio is disrupted in two mouse models of autism

Michelle C.D. Bridi, Nancy Luo, Grace Kim, Caroline O’Ferrall, Ruchit Patel, Sarah Bertrand, Sujatha Kannan, Alfredo Kirkwood
doi: https://doi.org/10.1101/2021.07.05.451213
Michelle C.D. Bridi
1Zanvyl Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, MD
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Nancy Luo
1Zanvyl Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, MD
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Grace Kim
1Zanvyl Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, MD
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Caroline O’Ferrall
2Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
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Ruchit Patel
2Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
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Sarah Bertrand
2Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
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Sujatha Kannan
2Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
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Alfredo Kirkwood
1Zanvyl Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, MD
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  • For correspondence: kirkwood@jhu.edu
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Abstract

Alterations to the balance between excitation and inhibition (E/I ratio) are postulated to underlie behavioral phenotypes in autism spectrum disorder (ASD) patients and mouse models. However, in wild type mice the E/I ratio is not constant, but instead oscillates across the 24h day. Therefore, we tested whether the E/I oscillation, rather than the overall E/I ratio, is disrupted in two ASD mouse lines: Fmr1 KO and BTBR, models of syndromic and idiopathic ASD, respectively. The E/I ratio is dysregulated in both models, but in different ways: the oscillation is flattened in Fmr1 KO and phase-shifted in BTBR mice. In both models these phenotypes associate with alterations in excitatory and inhibitory synaptic transmission and endocannabinoid signaling, but not with altered sleep. These findings suggest that ASD phenotypes may be produced by a mismatch of E/I to the appropriate behavioral state, rather than alterations to overall E/I levels per se.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Improved appearance of the figures

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted September 28, 2022.
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Daily oscillation of the excitation/inhibition ratio is disrupted in two mouse models of autism
Michelle C.D. Bridi, Nancy Luo, Grace Kim, Caroline O’Ferrall, Ruchit Patel, Sarah Bertrand, Sujatha Kannan, Alfredo Kirkwood
bioRxiv 2021.07.05.451213; doi: https://doi.org/10.1101/2021.07.05.451213
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Daily oscillation of the excitation/inhibition ratio is disrupted in two mouse models of autism
Michelle C.D. Bridi, Nancy Luo, Grace Kim, Caroline O’Ferrall, Ruchit Patel, Sarah Bertrand, Sujatha Kannan, Alfredo Kirkwood
bioRxiv 2021.07.05.451213; doi: https://doi.org/10.1101/2021.07.05.451213

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