{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T13:05:10Z","timestamp":1789218310450,"version":"build-2803163510"},"posted":{"date-parts":[[2026,1,28]]},"group-title":"Neuroscience","reference-count":72,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"award":["R01MH132586"],"award-info":[{"award-number":["R01MH132586"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01EY033950"],"award-info":[{"award-number":["R01EY033950"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01MH128176"],"award-info":[{"award-number":["R01MH128176"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["F31EY036279"],"award-info":[{"award-number":["F31EY036279"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["S10OD032336"],"award-info":[{"award-number":["S10OD032336"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,1,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    Cytoskeletal structure and neuronal function are heavily intertwined, and altered pyramidal neuron morphology (e.g., reduced dendritic arbors) has been consistently identified in the neocortex of individuals with psychiatric disorders. A missense mutation in\n                    <jats:italic>Kalrn<\/jats:italic>\n                    (\n                    <jats:italic>Kalrn<\/jats:italic>\n                    -PT) enhances activation of RhoA, a cytoskeletal regulator, and leads to adolescent-onset dendritic regression in supragranular auditory cortex. To investigate the relationship between this spatiotemporally altered cytoskeletal structure and psychiatric-relevant dysfunction, we examine the functional impacts of this genetic mutation, focusing on mismatch negativity \u2013 a common biomarker of altered sensory integration that matures across adolescence.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    In\n                    <jats:italic>Kalrn<\/jats:italic>\n                    -PT and littermate wild-type mice, pyramidal dendritic morphology was assessed across primary visual cortex (V1) layers using Golgi staining (n=172 neurons\/26 mice). Local field potentials (LFPs) and neuronal spiking were recorded during a visual oddball sequence (n=25 mice). Deviance detection \u2013 the rodent neural analogue of mismatch negativity \u2013 was analyzed across V1 layers.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Kalrn<\/jats:italic>\n                    -PT mice exhibit reductions in V1 dendritic length specific to layer 2\/3, mirroring observations in post-mortem samples from people with psychiatric disorders. Deviance detection was reduced in LFPs from\n                    <jats:italic>Kalrn<\/jats:italic>\n                    -PT mice and absent in layer 2\/3 neurons, despite typical feature selectivity and firing rates. These deficits were accompanied by reduced functional connectivity between visual and frontal areas.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>\n                    These results highlight alterations in higher-level sensory cortical integration in\n                    <jats:italic>Kalrn<\/jats:italic>\n                    -PT mice and demonstrate that adolescent-onset, disease-relevant structural and functional phenotypes can be linked by a common upstream effector. Further, these alterations appear restricted to supragranular layers, demonstrating an outsized role for\n                    <jats:italic>Kalrn<\/jats:italic>\n                    , particularly longer isoforms, in superficial neocortex.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.01.28.702244","type":"posted-content","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T08:05:16Z","timestamp":1769673916000},"source":"Crossref","is-referenced-by-count":1,"title":["A Key Regulator of Dendritic Morphology in Supragranular Neocortex Impacts Mismatch Negativity"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5304-2189","authenticated-orcid":false,"given":"Anna M.","family":"Rader Groves","sequence":"first","affiliation":[{"name":"Neuroscience Institute, Georgia State University, Atlanta, GA 30303"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3531-4213","authenticated-orcid":false,"given":"Connor G.","family":"Gallimore","sequence":"additional","affiliation":[{"name":"Neuroscience Institute, Georgia State University, Atlanta, GA 30303"},{"name":"Emotional Brain Institute, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10692"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina J.","family":"Sutton","sequence":"additional","affiliation":[{"name":"Neuroscience Institute, Georgia State University, Atlanta, GA 30303"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4345-0135","authenticated-orcid":false,"given":"Jordan M.","family":"Ross","sequence":"additional","affiliation":[{"name":"Neuroscience Institute, Georgia State University, Atlanta, GA 30303"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9154-9709","authenticated-orcid":false,"given":"Robert A.","family":"Sweet","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Translational Neuroscience Program, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie J.","family":"Grubisha","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Translational Neuroscience Program, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9868-6121","authenticated-orcid":false,"given":"Jordan P.","family":"Hamm","sequence":"additional","affiliation":[{"name":"Neuroscience Institute, Georgia State University, Atlanta, GA 30303"},{"name":"Emotional Brain Institute, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10692"},{"name":"Department of Psychiatry, New York University Grossman School of Medicine, New York, NY 10016"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026020504475135000_2026.01.28.702244v1.1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13123"},{"key":"2026020504475135000_2026.01.28.702244v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibtech.2018.09.007"},{"key":"2026020504475135000_2026.01.28.702244v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2018.16"},{"key":"2026020504475135000_2026.01.28.702244v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.04.044"},{"key":"2026020504475135000_2026.01.28.702244v1.5","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1001\/jamapsychiatry.2025.2221","article-title":"Regional specificity of cortical layer 3 dendritic spine deficits in schizophrenia","volume":"82","year":"2025","journal-title":"JAMA Psychiatry"},{"key":"2026020504475135000_2026.01.28.702244v1.6","doi-asserted-by":"crossref","first-page":"669","DOI":"10.3892\/etm.2021.10101","article-title":"Morphological alterations of the pyramidal and stellate cells of the visual cortex in schizophrenia","volume":"22","year":"2021","journal-title":"Exp Ther Med"},{"key":"2026020504475135000_2026.01.28.702244v1.7","doi-asserted-by":"crossref","first-page":"e780","DOI":"10.1038\/tp.2016.43","article-title":"Multiple markers of cortical morphology reveal evidence of supragranular thinning in schizophrenia","volume":"6","year":"2016","journal-title":"Transl Psychiatry"},{"key":"2026020504475135000_2026.01.28.702244v1.8","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.162.6.1200"},{"key":"2026020504475135000_2026.01.28.702244v1.9","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.104.008169"},{"key":"2026020504475135000_2026.01.28.702244v1.10","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abn8367"},{"key":"2026020504475135000_2026.01.28.702244v1.11","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01624-4"},{"key":"2026020504475135000_2026.01.28.702244v1.12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2022546118"},{"key":"2026020504475135000_2026.01.28.702244v1.13","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-200011090-00044"},{"key":"2026020504475135000_2026.01.28.702244v1.14","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbq118"},{"key":"2026020504475135000_2026.01.28.702244v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04556-w"},{"key":"2026020504475135000_2026.01.28.702244v1.16","doi-asserted-by":"publisher","DOI":"10.1126\/science.aay8833"},{"key":"2026020504475135000_2026.01.28.702244v1.17","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242115623"},{"key":"2026020504475135000_2026.01.28.702244v1.18","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1093\/cercor\/bhz070","article-title":": Dysregulated prefrontal cortical RhoA signal transduction in bipolar disorder with psychosis: New implications for disease pathophysiology","volume":"30","year":"2020","journal-title":"Cereb Cortex"},{"key":"2026020504475135000_2026.01.28.702244v1.19","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddx355"},{"key":"2026020504475135000_2026.01.28.702244v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2023.175648"},{"key":"2026020504475135000_2026.01.28.702244v1.21","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12261"},{"key":"2026020504475135000_2026.01.28.702244v1.22","doi-asserted-by":"crossref","first-page":"729076","DOI":"10.3389\/fcell.2021.729076","article-title":"Rho signaling in synaptic plasticity, memory, and brain disorders","volume":"9","year":"2021","journal-title":"Front Cell Dev Biol"},{"key":"2026020504475135000_2026.01.28.702244v1.23","doi-asserted-by":"crossref","unstructured":"Mitchell KJ , O\u2019Donnell P , Durstewitz D , Fenton AA , Gingrich JA , Gordon JA , et al. (2013): How Can Models Be Better Utilized to Enhance Outcome? In: Silverstein SM , Moghaddam B , Wykes T , editors. Schizophrenia: Evolution and Synthesis, vol. 13. Cambridge: MIT Press.","DOI":"10.7551\/mitpress\/9780262019620.003.0013"},{"key":"2026020504475135000_2026.01.28.702244v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2647"},{"key":"2026020504475135000_2026.01.28.702244v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(02)02807-X"},{"key":"2026020504475135000_2026.01.28.702244v1.26","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbr025"},{"key":"2026020504475135000_2026.01.28.702244v1.27","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awr064"},{"key":"2026020504475135000_2026.01.28.702244v1.28","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbp060"},{"key":"2026020504475135000_2026.01.28.702244v1.29","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.64.5.521"},{"key":"2026020504475135000_2026.01.28.702244v1.30","doi-asserted-by":"crossref","unstructured":"Curtis MT , Coffman BA , Salisbury DF (2021): Pitch and duration mismatch negativity are associated with distinct auditory cortex and inferior frontal cortex volumes in the first-episode schizophrenia spectrum. Schizophr Bull Open 2: sgab005.","DOI":"10.1093\/schizbullopen\/sgab005"},{"key":"2026020504475135000_2026.01.28.702244v1.31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2026179118"},{"key":"2026020504475135000_2026.01.28.702244v1.32","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhad215"},{"key":"2026020504475135000_2026.01.28.702244v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.10.038"},{"key":"2026020504475135000_2026.01.28.702244v1.34","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.09.024"},{"key":"2026020504475135000_2026.01.28.702244v1.35","doi-asserted-by":"crossref","first-page":"113133","DOI":"10.1016\/j.celrep.2023.113133","article-title":"Top-down input modulates visual context processing through an interneuron-specific circuit","volume":"42","year":"2023","journal-title":"Cell Rep"},{"key":"2026020504475135000_2026.01.28.702244v1.36","doi-asserted-by":"crossref","first-page":"115538","DOI":"10.1016\/j.celrep.2025.115538","article-title":"Top-down prediction signals from the medial prefrontal cortex govern auditory cortex prediction errors","volume":"44","year":"2025","journal-title":"Cell Rep"},{"key":"2026020504475135000_2026.01.28.702244v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-42553-3"},{"key":"2026020504475135000_2026.01.28.702244v1.38","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.02.006"},{"key":"2026020504475135000_2026.01.28.702244v1.39","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1016\/j.clinph.2015.06.026","article-title":"The maturation of mismatch negativity networks in normal adolescence","volume":"127","year":"2016","journal-title":"Clin Neurophysiol"},{"key":"2026020504475135000_2026.01.28.702244v1.40","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.schres.2017.09.047","article-title":": Developmental trajectory of mismatch negativity and visual event-related potentials in healthy controls: Implications for neurodevelopmental vs. neurodegenerative models of schizophrenia","volume":"191","year":"2018","journal-title":"Schizophr Res"},{"key":"2026020504475135000_2026.01.28.702244v1.41","doi-asserted-by":"publisher","DOI":"10.1111\/j.1467-7687.2010.00990.x"},{"key":"2026020504475135000_2026.01.28.702244v1.42","doi-asserted-by":"publisher","DOI":"10.1101\/2025.10.14.682114"},{"key":"2026020504475135000_2026.01.28.702244v1.43","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2008.67"},{"key":"2026020504475135000_2026.01.28.702244v1.44","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5198-11.2012"},{"key":"2026020504475135000_2026.01.28.702244v1.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.cortex.2016.03.017"},{"key":"2026020504475135000_2026.01.28.702244v1.46","doi-asserted-by":"crossref","first-page":"2863","DOI":"10.1111\/ejn.16355","article-title":"Systematic review and meta-analysis of the visual mismatch negativity in schizophrenia","volume":"59","year":"2024","journal-title":"Eur J Neurosci"},{"key":"2026020504475135000_2026.01.28.702244v1.47","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1038\/s41537-021-00156-1","article-title":"Increased face detection responses on the mooney faces test in people at clinical high risk for psychosis","volume":"7","year":"2021","journal-title":"NPJ Schizophr"},{"key":"2026020504475135000_2026.01.28.702244v1.48","doi-asserted-by":"crossref","first-page":"e13354","DOI":"10.1016\/j.heliyon.2023.e13354","article-title":"Visual processing deficits in patients with schizophrenia spectrum and bipolar disorders and associations with psychotic symptoms, and intellectual abilities","volume":"9","year":"2023","journal-title":"Heliyon"},{"key":"2026020504475135000_2026.01.28.702244v1.49","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-022-01385-3"},{"key":"2026020504475135000_2026.01.28.702244v1.50","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02038-6"},{"key":"2026020504475135000_2026.01.28.702244v1.51","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbaa006"},{"key":"2026020504475135000_2026.01.28.702244v1.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2008.03.014"},{"key":"2026020504475135000_2026.01.28.702244v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2017.11.029"},{"key":"2026020504475135000_2026.01.28.702244v1.54","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2011.11.003"},{"key":"2026020504475135000_2026.01.28.702244v1.55","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1038\/s41398-017-0045-y","article-title":"Actin polymerization is reduced in the anterior cingulate cortex of elderly patients with schizophrenia","volume":"7","year":"2017","journal-title":"Transl Psychiatry"},{"key":"2026020504475135000_2026.01.28.702244v1.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2014.12.029"},{"key":"2026020504475135000_2026.01.28.702244v1.57","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001792"},{"key":"2026020504475135000_2026.01.28.702244v1.58","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.01.010"},{"key":"2026020504475135000_2026.01.28.702244v1.59","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2022.110416"},{"key":"2026020504475135000_2026.01.28.702244v1.60","doi-asserted-by":"publisher","DOI":"10.1038\/S41586-022-04434-5"},{"key":"2026020504475135000_2026.01.28.702244v1.61","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.103620"},{"key":"2026020504475135000_2026.01.28.702244v1.62","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/s41398-020-00917-z","article-title":"ARHGAP10, which encodes Rho GTPase-activating protein 10, is a novel gene for schizophrenia risk","volume":"10","year":"2020","journal-title":"Transl Psychiatry"},{"key":"2026020504475135000_2026.01.28.702244v1.63","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4216"},{"key":"2026020504475135000_2026.01.28.702244v1.64","doi-asserted-by":"crossref","first-page":"D147","DOI":"10.1093\/nar\/gkaf1238","article-title":": Expression Atlas in 2026: enabling FAIR and open expression data through community collaboration and integration","volume":"54","year":"2026","journal-title":"Nucleic Acids Res"},{"key":"2026020504475135000_2026.01.28.702244v1.65","doi-asserted-by":"publisher","DOI":"10.1038\/nature05453"},{"key":"2026020504475135000_2026.01.28.702244v1.66","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2006.07.033"},{"key":"2026020504475135000_2026.01.28.702244v1.67","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.161.4.742"},{"key":"2026020504475135000_2026.01.28.702244v1.68","doi-asserted-by":"publisher","DOI":"10.1016\/S0920-9964(02)00201-3"},{"key":"2026020504475135000_2026.01.28.702244v1.69","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0404-13.2013"},{"key":"2026020504475135000_2026.01.28.702244v1.70","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/s41398-023-02393-7","article-title":"Mouse mutants in schizophrenia risk genes GRIN2A and AKAP11 show EEG abnormalities in common with schizophrenia patients","volume":"13","year":"2023","journal-title":"Transl Psychiatry"},{"key":"2026020504475135000_2026.01.28.702244v1.71","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2019.02.017"},{"key":"2026020504475135000_2026.01.28.702244v1.72","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.07.065"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.01.28.702244","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T12:48:01Z","timestamp":1770295681000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.01.28.702244"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,28]]},"references-count":72,"URL":"https:\/\/doi.org\/10.64898\/2026.01.28.702244","relation":{},"subject":[],"published":{"date-parts":[[2026,1,28]]},"subtype":"preprint"}}