{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T21:04:01Z","timestamp":1782421441420,"version":"3.54.5"},"posted":{"date-parts":[[2025,3,6]]},"group-title":"Neuroscience","reference-count":51,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Homeostatic plasticity is essential for information processing and the stability of neuronal circuits, however its relevance to neuropsychiatric disorders remains unclear. The 16p11.2 duplication (BP4-BP5) is a genetic risk factor that strongly predisposes to a range of severe mental illnesses including autism, schizophrenia, intellectual disability, and epilepsy. The duplication consists of a 600 kb region on chromosome 16, including 27 protein-coding genes, with poorly defined effects on neuronal structure and function. Here, we used a mouse model of the 16p11.2 duplication to investigate the impact of this variant on synaptic structure and downstream homeostatic plasticity. We find that 16p11.2 duplication neurons exhibit overly branched dendritic arbors and excessive spine numbers, which host an overabundance of surface AMPA receptor subunit GluA1. Using a homeostatic plasticity paradigm, we show that 16p11.2 duplication neurons fail to undergo synaptic upscaling upon activity deprivation, consistent with disrupted structural plasticity. We also observe that the increased surface abundance of GluA1 occludes further insertion events, a critical mechanism for synaptic plasticity. Finally, we show that genetically correcting the dosage of 16p11.2-encoded\n                  <jats:italic>Prrt2<\/jats:italic>\n                  to wild-type levels rescues structural spine phenotypes. Our work suggests that aberrant plasticity could contribute to the etiology of neuropsychiatric disorders.\n                <\/jats:p>","DOI":"10.1101\/2025.03.06.641931","type":"posted-content","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T07:44:01Z","timestamp":1741333441000},"source":"Crossref","is-referenced-by-count":2,"title":["Impairment of homeostatic structural plasticity caused by the autism and schizophrenia-associated 16p11.2 duplication"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9280-7850","authenticated-orcid":false,"given":"MP","family":"Forrest","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA"},{"name":"Center for Autism and Neurodevelopment, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"NH","family":"Piguel","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA"},{"name":"Center for Autism and Neurodevelopment, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"VA","family":"Bagchi","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"LE","family":"Dionisio","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S","family":"Yoon","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA"},{"name":"Center for Autism and Neurodevelopment, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Dos Santos","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA"},{"name":"Center for Autism and Neurodevelopment, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MS","family":"LeDoux","sequence":"additional","affiliation":[{"name":"Department of Psychology, University of Memphis, Memphis, TN, 38152, USA"},{"name":"Veracity Neuroscience LLC, Memphis, TN, 38157, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P","family":"Penzes","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA"},{"name":"Center for Autism and Neurodevelopment, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041112362961000_2025.03.06.641931v1.1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2019.3360"},{"key":"2026041112362961000_2025.03.06.641931v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)31129-2"},{"key":"2026041112362961000_2025.03.06.641931v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nature13772"},{"key":"2026041112362961000_2025.03.06.641931v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3992"},{"key":"2026041112362961000_2025.03.06.641931v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/S41586-022-04434-5"},{"key":"2026041112362961000_2025.03.06.641931v1.6","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2018.16"},{"key":"2026041112362961000_2025.03.06.641931v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.02.017"},{"key":"2026041112362961000_2025.03.06.641931v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/nature11860"},{"key":"2026041112362961000_2025.03.06.641931v1.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2020.09.001"},{"key":"2026041112362961000_2025.03.06.641931v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36087-x"},{"key":"2026041112362961000_2025.03.06.641931v1.11","doi-asserted-by":"crossref","unstructured":"Savino E , Cervigni RI , Povolo M , Stefanetti A , Ferrante D , Valente P , et al. 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