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To determine the neurobiological functions of AKAP11, we conduct multi-omic and neurobiological analyses of\n                  <jats:italic>Akap11<\/jats:italic>\n                  mutant mouse brains. We find that AKAP11 is a key regulator of PKA proteostasis in the brain whose loss leads to dramatically increased levels of PKA subunits and phosphorylated PKA substrates, especially in synapses.\n                  <jats:italic>Akap11<\/jats:italic>\n                  mutant mice show extensive transcriptomic changes throughout the brain, including prominent decreases in synapse-related genes sets. Gene expression is highly impacted in spiny projection neurons of the striatum, a brain region implicated in motivation, cognition and psychotic disorders. Real-time measurements of PKA activity reveal elevated basal PKA activity in the striatum of\n                  <jats:italic>\n                    Akap11\n                    <jats:sup>-\/-<\/jats:sup>\n                  <\/jats:italic>\n                  mice, with exaggerated additional response to dopamine receptor antagonists. Behaviorally,\n                  <jats:italic>Akap11<\/jats:italic>\n                  mutant mice show abnormally prolonged locomotor response to amphetamine, deficits in associative learning and contextual discrimination, as well as depression-like behaviors. Our study connects molecular changes to circuit dysfunction and behavioral disturbance in a genetically valid animal model of psychotic disorder.\n                <\/jats:p>","DOI":"10.1101\/2024.09.24.614783","type":"posted-content","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T23:50:11Z","timestamp":1727221811000},"source":"Crossref","is-referenced-by-count":10,"title":["Elevated synaptic PKA activity and abnormal striatal dopamine signaling in\n                  <i>Akap11<\/i>\n                  mutant mice, a genetic model of schizophrenia and bipolar disorder"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0549-4823","authenticated-orcid":false,"given":"Bryan J.","family":"Song","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3139-9053","authenticated-orcid":false,"given":"Yang","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2175-6312","authenticated-orcid":false,"given":"Ally","family":"Nicolella","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Jee","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Lodder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6712-9277","authenticated-orcid":false,"given":"Kevin","family":"Bonanno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antia","family":"Valle-Tojeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nolan D.","family":"Hartley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6262-6904","authenticated-orcid":false,"given":"Kira Perzel","family":"Mandell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Adeleye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deeksha","family":"Misri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuhan","family":"Geng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahana","family":"Natarajan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In\u00e8s","family":"Picard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8629-3152","authenticated-orcid":false,"given":"Nate","family":"Shepard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa","family":"Hall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawen","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3577-4383","authenticated-orcid":false,"given":"Sameer","family":"Aryal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7274-981X","authenticated-orcid":false,"given":"Zohreh","family":"Farsi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9968-3988","authenticated-orcid":false,"given":"Xiao-Man","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0346-9651","authenticated-orcid":false,"given":"Nader","family":"Morshed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7805-8523","authenticated-orcid":false,"given":"Naeem M","family":"Nadaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8455-1966","authenticated-orcid":false,"given":"Horia","family":"Pribiag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1537-4000","authenticated-orcid":false,"given":"Sean K","family":"Simmons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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