{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T08:51:22Z","timestamp":1775983882138,"version":"3.50.1"},"posted":{"date-parts":[[2025,3,29]]},"group-title":"Neuroscience","reference-count":39,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T00:00:00Z","timestamp":1743206400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,29]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>Synaptic dysfunction has been implicated as a key mechanism underlying the pathophysiology of psychiatric disorders. Most pharmacological therapeutics for schizophrenia, autism spectrum disorder, obsessive-compulsive disorder, and major depressive disorder temporarily augment chemical synapse function. Nevertheless, medication non-compliance is a major clinical challenge, and behavioral dysfunction often returns following pharmacotherapeutic discontinuation. Here, we deployed a designer electrical synapse to edit a single class of chemical synapses in a genetic mouse model of obsessive-compulsive disorder (OCD). Editing these synapses in juvenile mice normalized circuit function and prevented the emergence of pathological repetitive behavior in adulthood. Thus, we establish precision circuit editing as a putative strategy for preventative psychotherapeutics.<\/jats:p>","DOI":"10.1101\/2025.03.27.645613","type":"posted-content","created":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T02:22:33Z","timestamp":1743301353000},"source":"Crossref","is-referenced-by-count":0,"title":["Synaptic editing of frontostriatal circuitry prevents excessive grooming in SAPAP3-deficient mice"],"prefix":"10.64898","author":[{"given":"Kathryn K.","family":"Walder-Christensen","sequence":"first","affiliation":[{"name":"Dept. of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina 27710, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah A.","family":"Soliman","sequence":"additional","affiliation":[{"name":"Dept. of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina 27710, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9918-3294","authenticated-orcid":false,"given":"Nicole","family":"Calakos","sequence":"additional","affiliation":[{"name":"Dept. of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA"},{"name":"Dept. of Neurology, Duke University Medical Center, Durham, North Carolina 27710, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4280-9994","authenticated-orcid":false,"given":"Kafui","family":"Dzirasa","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA"},{"name":"Dept. of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina 27710, USA"},{"name":"Dept. of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, USA"},{"name":"Dept. of Neurosurgery, Duke University Medical Center, Durham, North Carolina 27710, USA"},{"name":"Dept. of Biomedical Engineering, Duke University, Durham North Carolina 27708, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026041201283014000_2025.03.27.645613v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-022-01370-w"},{"key":"2026041201283014000_2025.03.27.645613v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-024-01943-x"},{"key":"2026041201283014000_2025.03.27.645613v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2019.01.004"},{"key":"2026041201283014000_2025.03.27.645613v1.4","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-018-0518-5"},{"key":"2026041201283014000_2025.03.27.645613v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.12.040"},{"key":"2026041201283014000_2025.03.27.645613v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2017.03.010"},{"key":"2026041201283014000_2025.03.27.645613v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/nature06104"},{"key":"2026041201283014000_2025.03.27.645613v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbrainres.2004.03.014"},{"key":"2026041201283014000_2025.03.27.645613v1.9","doi-asserted-by":"publisher","DOI":"10.3390\/cells11233815"},{"key":"2026041201283014000_2025.03.27.645613v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/S0193-953X(05)70181-7"},{"key":"2026041201283014000_2025.03.27.645613v1.11","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awm205"},{"key":"2026041201283014000_2025.03.27.645613v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpr.2005.06.010"},{"key":"2026041201283014000_2025.03.27.645613v1.13","doi-asserted-by":"publisher","DOI":"10.1503\/jpn.130220"},{"key":"2026041201283014000_2025.03.27.645613v1.14","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2009.152"},{"key":"2026041201283014000_2025.03.27.645613v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2013.06.013"},{"key":"2026041201283014000_2025.03.27.645613v1.16","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-022-01588-6"},{"key":"2026041201283014000_2025.03.27.645613v1.17","doi-asserted-by":"publisher","DOI":"10.1126\/science.1232380"},{"key":"2026041201283014000_2025.03.27.645613v1.18","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01633-3"},{"key":"2026041201283014000_2025.03.27.645613v1.19","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0789-4"},{"key":"2026041201283014000_2025.03.27.645613v1.20","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0764-10.2010"},{"key":"2026041201283014000_2025.03.27.645613v1.21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2010.11.014"},{"key":"2026041201283014000_2025.03.27.645613v1.22","doi-asserted-by":"publisher","DOI":"10.1101\/2025.03.25.645291"},{"key":"2026041201283014000_2025.03.27.645613v1.23","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.02.028"},{"key":"2026041201283014000_2025.03.27.645613v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5537"},{"key":"2026041201283014000_2025.03.27.645613v1.25","unstructured":"Brock, H. , Rizvi, A. & Hany, M. in StatPearls (2025)."},{"key":"2026041201283014000_2025.03.27.645613v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpr.2015.06.003"},{"key":"2026041201283014000_2025.03.27.645613v1.27","doi-asserted-by":"publisher","DOI":"10.1002\/da.22103"},{"key":"2026041201283014000_2025.03.27.645613v1.28","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0102-3"},{"key":"2026041201283014000_2025.03.27.645613v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1024-7"},{"key":"2026041201283014000_2025.03.27.645613v1.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.05.028"},{"key":"2026041201283014000_2025.03.27.645613v1.31","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-024-02451-6"},{"key":"2026041201283014000_2025.03.27.645613v1.32","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.15312"},{"key":"2026041201283014000_2025.03.27.645613v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2996"},{"key":"2026041201283014000_2025.03.27.645613v1.34","doi-asserted-by":"publisher","DOI":"10.1101\/2024.06.26.600900"},{"key":"2026041201283014000_2025.03.27.645613v1.35","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4289-10.2010"},{"key":"2026041201283014000_2025.03.27.645613v1.36","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11459"},{"key":"2026041201283014000_2025.03.27.645613v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-024-02232-7"},{"key":"2026041201283014000_2025.03.27.645613v1.38","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0971-11.2011"},{"key":"2026041201283014000_2025.03.27.645613v1.39","unstructured":"Institute, A. <https:\/\/allensdk.readthedocs.io\/en\/latest\/_static\/examples\/nb\/ecephys_quality_metrics.html> ("}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.03.27.645613","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T08:28:37Z","timestamp":1775982517000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2025.03.27.645613"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,29]]},"references-count":39,"URL":"https:\/\/doi.org\/10.1101\/2025.03.27.645613","relation":{},"subject":[],"published":{"date-parts":[[2025,3,29]]},"subtype":"preprint"}}