{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T19:32:38Z","timestamp":1781119958934,"version":"3.54.1"},"reference-count":108,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T00:00:00Z","timestamp":1672099200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["202397\/Z\/16\/Z"],"award-info":[{"award-number":["202397\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000288","name":"Royal Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000288","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Hypothesis<\/jats:title><jats:p>Converging lines of evidence suggest that dysfunction of cortical GABAergic inhibitory interneurons is a core feature of psychosis. This dysfunction is thought to underlie neuroimaging abnormalities commonly found in patients with psychosis, particularly in the hippocampus. These include increases in resting cerebral blood flow (CBF) and glutamatergic metabolite levels, and decreases in ligand binding to GABAA \u03b15 receptors and to the synaptic density marker synaptic vesicle glycoprotein 2A (SV2A). However, direct links between inhibitory interneuron dysfunction and these neuroimaging readouts are yet to be established. Conditional deletion of a schizophrenia susceptibility gene, the tyrosine kinase receptor Erbb4, from cortical and hippocampal inhibitory interneurons leads to synaptic defects, and behavioral and cognitive phenotypes relevant to psychosis in mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Study Design<\/jats:title><jats:p>Here, we investigated how this inhibitory interneuron disruption affects hippocampal in vivo neuroimaging readouts. Adult Erbb4 conditional mutant mice (Lhx6-Cre;Erbb4F\/F, n = 12) and their wild-type littermates (Erbb4F\/F, n = 12) were scanned in a 9.4T magnetic resonance scanner to quantify CBF and glutamatergic metabolite levels (glutamine, glutamate, GABA). Subsequently, we assessed GABAA receptors and SV2A density using quantitative autoradiography.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Erbb4 mutant mice showed significantly elevated ventral hippccampus CBF and glutamine levels, and decreased SV2A density across hippocampus sub-regions compared to wild-type littermates. No significant GABAA receptor density differences were identified.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings demonstrate that specific disruption of cortical inhibitory interneurons in mice recapitulate some of the key neuroimaging findings in patients with psychosis, and link inhibitory interneuron deficits to non-invasive measures of brain function and neurochemistry that can be used across species.<\/jats:p><\/jats:sec>","DOI":"10.1093\/schbul\/sbac192","type":"journal-article","created":{"date-parts":[[2022,12,27]],"date-time":"2022-12-27T12:31:05Z","timestamp":1672144265000},"page":"569-580","source":"Crossref","is-referenced-by-count":10,"title":["<i>Erbb4<\/i>Deletion From Inhibitory Interneurons Causes Psychosis-Relevant Neuroimaging Phenotypes"],"prefix":"10.1093","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6819-8090","authenticated-orcid":false,"given":"Amanda","family":"Kiemes","sequence":"first","affiliation":[{"name":"Department of Psychosis Studies, Institute of Psychiatry, Psychology, and Neuroscience, King\u2019s College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Elisa","family":"Serrano Navacerrada","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging, School of Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King\u2019s College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging, School of Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King\u2019s College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Randall","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging, School of Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King\u2019s College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camilla","family":"Simmons","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging, School of Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King\u2019s College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loreto","family":"Rojo Gonzalez","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging, School of Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King\u2019s College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija-Magdalena","family":"Petrinovic","sequence":"additional","affiliation":[{"name":"MRC Centre for Neurodevelopmental Disorders, King\u2019s College London , London , UK"},{"name":"Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, Psychology, and Neuroscience, King\u2019s College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J","family":"Lythgoe","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging, School of Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King\u2019s College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Rotaru","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging, School of Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King\u2019s College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Di Censo","sequence":"additional","affiliation":[{"name":"Department of Neuroimaging, School of Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King\u2019s College London , London , UK"},{"name":"Department of Psychology, University of Cambridge , Cambridge , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydiane","family":"Hirschler","sequence":"additional","affiliation":[{"name":"C.J. Gorter Center for High Field MRI, Department of Radiology, Leiden University Medical Center , Leiden , The Netherlands"},{"name":"Univ. Grenoble Alpes, Inserm, U1216, Grenoble Institut Neurosciences , Grenoble , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel L","family":"Barbier","sequence":"additional","affiliation":[{"name":"Univ. Grenoble Alpes, Inserm, U1216, Grenoble Institut Neurosciences , Grenoble , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony C","family":"Vernon","sequence":"additional","affiliation":[{"name":"MRC Centre for Neurodevelopmental Disorders, King\u2019s College London , London , UK"},{"name":"Department of Basic and Clinical Neuroscience, School of Neuroscience, Institute of Psychiatry, Psychology, and Neuroscience, King\u2019s College London , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3051-0135","authenticated-orcid":false,"given":"James M","family":"Stone","sequence":"additional","affiliation":[{"name":"Brighton and Sussex Medical School, University of Sussex , Brighton , 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