Daily oscillation of the excitation/inhibition ratio is disrupted in two mouse models of autism
Summary: Alterations to the excitation/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 24-h day. Therefore, we tested wheth...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-01-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224027214 |
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| author | Michelle C.D. Bridi Nancy Luo Grace Kim Benjamin J. Menarchek Rachel A. Lee Bryan Rodriguez Daniel Severin Christian Wesselborg Caroline O’Ferrall Ruchit Patel Sarah Bertrand Sujatha Kannan Alfredo Kirkwood Cristian Moreno Altagracia Contreras |
| author_facet | Michelle C.D. Bridi Nancy Luo Grace Kim Benjamin J. Menarchek Rachel A. Lee Bryan Rodriguez Daniel Severin Christian Wesselborg Caroline O’Ferrall Ruchit Patel Sarah Bertrand Sujatha Kannan Alfredo Kirkwood Cristian Moreno Altagracia Contreras |
| author_sort | Michelle C.D. Bridi |
| collection | DOAJ |
| description | Summary: Alterations to the excitation/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 24-h day. Therefore, we tested whether E/I regulation, rather than the overall E/I ratio, is disrupted in two ASD-related 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 lost in Fmr1 KO and reversed in BTBR mice. Phenotypes in both models associate with differences the timing of excitatory and inhibitory synaptic transmission and endocannabinoid signaling compared to wild type mice, but not with altered sleep. These findings raise the possibility that ASD-related phenotypes may be produced by a mismatch between E/I and behavioral state, rather than alterations to overall E/I levels per se. |
| format | Article |
| id | doaj-art-6184046b90a74b38b186d7b126c7fe86 |
| institution | Kabale University |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-6184046b90a74b38b186d7b126c7fe862025-01-04T04:56:48ZengElsevieriScience2589-00422025-01-01281111494Daily oscillation of the excitation/inhibition ratio is disrupted in two mouse models of autismMichelle C.D. Bridi0Nancy Luo1Grace Kim2Benjamin J. Menarchek3Rachel A. Lee4Bryan Rodriguez5Daniel Severin6Christian Wesselborg7Caroline O’Ferrall8Ruchit Patel9Sarah Bertrand10Sujatha Kannan11Alfredo Kirkwood12Cristian Moreno13Altagracia Contreras14Zanvyl Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, MD, USA; Department of Neuroscience, West Virginia University, Morgantown, WV, USA; Corresponding authorZanvyl Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, MD, USAZanvyl Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, MD, USADepartment of Neuroscience, West Virginia University, Morgantown, WV, USADepartment of Neuroscience, West Virginia University, Morgantown, WV, USADepartment of Neuroscience, West Virginia University, Morgantown, WV, USAZanvyl Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, MD, USAZanvyl Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, MD, USADepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USADepartment of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USAZanvyl Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, MD, USA; Corresponding authorZanvyl Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, MD, USAZanvyl Krieger Mind/Brain Institute, Johns Hopkins University, Baltimore, MD, USASummary: Alterations to the excitation/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 24-h day. Therefore, we tested whether E/I regulation, rather than the overall E/I ratio, is disrupted in two ASD-related 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 lost in Fmr1 KO and reversed in BTBR mice. Phenotypes in both models associate with differences the timing of excitatory and inhibitory synaptic transmission and endocannabinoid signaling compared to wild type mice, but not with altered sleep. These findings raise the possibility that ASD-related phenotypes may be produced by a mismatch between E/I and behavioral state, rather than alterations to overall E/I levels per se.http://www.sciencedirect.com/science/article/pii/S2589004224027214NeuroscienceSensory neuroscience |
| spellingShingle | Michelle C.D. Bridi Nancy Luo Grace Kim Benjamin J. Menarchek Rachel A. Lee Bryan Rodriguez Daniel Severin Christian Wesselborg Caroline O’Ferrall Ruchit Patel Sarah Bertrand Sujatha Kannan Alfredo Kirkwood Cristian Moreno Altagracia Contreras Daily oscillation of the excitation/inhibition ratio is disrupted in two mouse models of autism iScience Neuroscience Sensory neuroscience |
| title | Daily oscillation of the excitation/inhibition ratio is disrupted in two mouse models of autism |
| title_full | Daily oscillation of the excitation/inhibition ratio is disrupted in two mouse models of autism |
| title_fullStr | Daily oscillation of the excitation/inhibition ratio is disrupted in two mouse models of autism |
| title_full_unstemmed | Daily oscillation of the excitation/inhibition ratio is disrupted in two mouse models of autism |
| title_short | Daily oscillation of the excitation/inhibition ratio is disrupted in two mouse models of autism |
| title_sort | daily oscillation of the excitation inhibition ratio is disrupted in two mouse models of autism |
| topic | Neuroscience Sensory neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224027214 |
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