{"oa_version":"Published Version","volume":22,"date_updated":"2024-06-17T08:58:00Z","publication":"PLoS Biology","related_material":{"record":[{"id":"15385","status":"public","relation":"research_data"}],"link":[{"relation":"software","url":"https://doi.org/10.5281/zenodo.11130587"}]},"article_type":"original","quality_controlled":"1","oa":1,"scopus_import":"1","title":"Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice","ddc":["570"],"language":[{"iso":"eng"}],"type":"journal_article","publication_status":"epub_ahead","month":"06","project":[{"call_identifier":"H2020","_id":"2634E9D2-B435-11E9-9278-68D0E5697425","name":"Circuits of Visual Attention","grant_number":"756502"}],"citation":{"chicago":"Burnett, Laura, Peter Koppensteiner, Olga Symonova, Tomas Masson, Tomas A Vega Zuniga, Ximena Contreras, Thomas Rülicke, Ryuichi Shigemoto, Gaia Novarino, and Maximilian A Jösch. “Shared Behavioural Impairments in Visual Perception and Place Avoidance across Different Autism Models Are Driven by Periaqueductal Grey Hypoexcitability in Setd5 Haploinsufficient Mice.” <i>PLoS Biology</i>. Public Library of Science, 2024. <a href=\"https://doi.org/10.1371/journal.pbio.3002668\">https://doi.org/10.1371/journal.pbio.3002668</a>.","mla":"Burnett, Laura, et al. “Shared Behavioural Impairments in Visual Perception and Place Avoidance across Different Autism Models Are Driven by Periaqueductal Grey Hypoexcitability in Setd5 Haploinsufficient Mice.” <i>PLoS Biology</i>, vol. 22, e3002668, Public Library of Science, 2024, doi:<a href=\"https://doi.org/10.1371/journal.pbio.3002668\">10.1371/journal.pbio.3002668</a>.","ama":"Burnett L, Koppensteiner P, Symonova O, et al. Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice. <i>PLoS Biology</i>. 2024;22. doi:<a href=\"https://doi.org/10.1371/journal.pbio.3002668\">10.1371/journal.pbio.3002668</a>","ieee":"L. Burnett <i>et al.</i>, “Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice,” <i>PLoS Biology</i>, vol. 22. Public Library of Science, 2024.","ista":"Burnett L, Koppensteiner P, Symonova O, Masson T, Vega Zuniga TA, Contreras X, Rülicke T, Shigemoto R, Novarino G, Jösch MA. 2024. Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice. PLoS Biology. 22, e3002668.","apa":"Burnett, L., Koppensteiner, P., Symonova, O., Masson, T., Vega Zuniga, T. A., Contreras, X., … Jösch, M. A. (2024). Shared behavioural impairments in visual perception and place avoidance across different autism models are driven by periaqueductal grey hypoexcitability in Setd5 haploinsufficient mice. <i>PLoS Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pbio.3002668\">https://doi.org/10.1371/journal.pbio.3002668</a>","short":"L. Burnett, P. Koppensteiner, O. Symonova, T. Masson, T.A. Vega Zuniga, X. Contreras, T. Rülicke, R. Shigemoto, G. Novarino, M.A. Jösch, PLoS Biology 22 (2024)."},"ec_funded":1,"status":"public","_id":"17142","publisher":"Public Library of Science","article_processing_charge":"Yes","article_number":"e3002668","date_created":"2024-06-16T22:01:05Z","doi":"10.1371/journal.pbio.3002668","has_accepted_license":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"author":[{"last_name":"Burnett","first_name":"Laura","full_name":"Burnett, Laura","id":"3B717F68-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8937-410X"},{"first_name":"Peter","last_name":"Koppensteiner","orcid":"0000-0002-3509-1948","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","full_name":"Koppensteiner, Peter"},{"last_name":"Symonova","first_name":"Olga","full_name":"Symonova, Olga","id":"3C0C7BC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2012-9947"},{"last_name":"Masson","first_name":"Tomas","id":"93ac43e8-8599-11eb-9b86-f6efb0a4c207","full_name":"Masson, Tomas","orcid":"0000-0002-2634-6283"},{"id":"2E7C4E78-F248-11E8-B48F-1D18A9856A87","full_name":"Vega Zuniga, Tomas A","first_name":"Tomas A","last_name":"Vega Zuniga"},{"first_name":"Ximena","last_name":"Contreras","full_name":"Contreras, Ximena","id":"475990FE-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Rülicke, Thomas","first_name":"Thomas","last_name":"Rülicke"},{"first_name":"Ryuichi","last_name":"Shigemoto","orcid":"0000-0001-8761-9444","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi"},{"last_name":"Novarino","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178"},{"full_name":"Jösch, Maximilian A","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3937-1330","last_name":"Jösch","first_name":"Maximilian A"}],"acknowledgement":"This work was supported by a European Research Council Starting Grant 756502 (MJ). ","day":"10","date_published":"2024-06-10T00:00:00Z","publication_identifier":{"issn":["1544-9173"],"eissn":["1545-7885"]},"year":"2024","main_file_link":[{"url":"https://doi.org/10.1371/journal.pbio.3002668","open_access":"1"}],"department":[{"_id":"RySh"},{"_id":"GaNo"},{"_id":"MaJö"}],"abstract":[{"text":"Despite the diverse genetic origins of autism spectrum disorders (ASDs), affected individuals share strikingly similar and correlated behavioural traits that include perceptual and sensory processing challenges. Notably, the severity of these sensory symptoms is often predictive of the expression of other autistic traits. However, the origin of these perceptual deficits remains largely elusive. Here, we show a recurrent impairment in visual threat perception that is similarly impaired in 3 independent mouse models of ASD with different molecular aetiologies. Interestingly, this deficit is associated with reduced avoidance of threatening environments—a nonperceptual trait. Focusing on a common cause of ASDs, the Setd5 gene mutation, we define the molecular mechanism. We show that the perceptual impairment is caused by a potassium channel (Kv1)-mediated hypoexcitability in a subcortical node essential for the initiation of escape responses, the dorsal periaqueductal grey (dPAG). Targeted pharmacological Kv1 blockade rescued both perceptual and place avoidance deficits, causally linking seemingly unrelated trait deficits to the dPAG. Furthermore, we show that different molecular mechanisms converge on similar behavioural phenotypes by demonstrating that the autism models Cul3 and Ptchd1, despite having similar behavioural phenotypes, differ in their functional and molecular alteration. Our findings reveal a link between rapid perception controlled by subcortical pathways and appropriate learned interactions with the environment and define a nondevelopmental source of such deficits in ASD.","lang":"eng"}],"intvolume":"        22"}