{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T17:19:55Z","timestamp":1787678395053,"version":"build-2784847793"},"reference-count":51,"publisher":"National Academy of Sciences","issue":"35","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"HHS | NIH | National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01MH107182"],"award-info":[{"award-number":["R01MH107182"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"HHS | NIH | National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA060553"],"award-info":[{"award-number":["P30 CA060553"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"HHS | NIH | National Institute of Mental Health","doi-asserted-by":"publisher","award":["1S10OD032270-01"],"award-info":[{"award-number":["1S10OD032270-01"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">ANK3<\/jats:italic>\n                    , encoding the scaffolding protein ankyrin-G, is a major risk gene for bipolar disorder and schizophrenia, but its cellular and circuit-level mechanisms remain poorly defined. Here, we demonstrate that deletion of\n                    <jats:italic toggle=\"yes\">Ank3<\/jats:italic>\n                    in forebrain excitatory neurons-either prenatally (\n                    <jats:italic toggle=\"yes\">\n                      Ank3\n                      <jats:sup>\u2013\/<\/jats:sup>\n                      <jats:sup>\u2212<\/jats:sup>\n                      :Emx1-Cre\n                    <\/jats:italic>\n                    ) or in adolescence (\n                    <jats:italic toggle=\"yes\">\n                      Ank3\n                      <jats:sup>\u2013\/<\/jats:sup>\n                      <jats:sup>\u2013<\/jats:sup>\n                      :CaMKII\u03b1-Cre\n                    <\/jats:italic>\n                    ) leads to convergent behavioral phenotypes in adulthood, including hyperactivity, reduced anxiety-like behavior, and decreased depression-like responses. Calcium imaging in cultured neurons and acute brain slices revealed that ankyrin-G loss reduces both spontaneous and evoked neuronal activity. Quantitative proteomic profiling of membrane-enriched cortical fractions uncovered widespread remodeling of the synaptic proteome, including upregulation of the kinase Taok2 and unexpected downregulation of myelin basic protein (Mbp), a structural component of oligodendrocyte-derived myelin. Importantly, chronic lithium treatment, known to reverse behavioral abnormalities in\n                    <jats:italic toggle=\"yes\">Ank3<\/jats:italic>\n                    -deficient mice, also restored Mbp expression. Together, our findings identify ankyrin-G as a molecular bridge between excitatory neuronal activity, synaptic structure, and myelin-associated protein expression, revealing a pathway by which\n                    <jats:italic toggle=\"yes\">ANK3<\/jats:italic>\n                    variants may contribute to neuropsychiatric disease.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2606900123","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T16:36:09Z","timestamp":1787675769000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["<i>Ank3<\/i>\n                    loss in adult forebrain excitatory neurons disrupts behavior, neuronal activity, membrane proteome, and myelination"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6545-3615","authenticated-orcid":false,"given":"Sehyoun","family":"Yoon","sequence":"first","affiliation":[{"name":"Department of Neuroscience, Northwestern University Feinberg School of Medicine","place":["Chicago"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6101-5631","authenticated-orcid":false,"given":"Marc Dos","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Northwestern University Feinberg School of Medicine","place":["Chicago"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Khalatyan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Northwestern University Feinberg School of Medicine","place":["Chicago"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8173-5580","authenticated-orcid":false,"given":"Jeffrey N.","family":"Savas","sequence":"additional","affiliation":[{"name":"Department of Neurology, Northwestern University Feinberg School of Medicine","place":["Chicago"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5449-1640","authenticated-orcid":false,"given":"Peter","family":"Penzes","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Northwestern University Feinberg School of Medicine","place":["Chicago"]},{"name":"Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine","place":["Chicago"]},{"name":"Department of Pharmacology, Northwestern University Feinberg School of Medicine","place":["Chicago"]},{"name":"Center for Autism and Neurodevelopment, Northwestern University Feinberg School 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