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Via stereology and single nucleus transcriptomics (snRNA-seq), we found increased\n                  <jats:italic>\n                    Chd8\n                    <jats:sup>+\/-<\/jats:sup>\n                  <\/jats:italic>\n                  cortical volume was not explained by increase in neuron number. Differential expression (DE) was present across cortical cell types, with excitatory neurons exhibiting high DE burden and shared and subclass-specific DE signatures. Bulk RNA-seq DE of constitutive\n                  <jats:italic>\n                    Chd8\n                    <jats:sup>+\/-<\/jats:sup>\n                  <\/jats:italic>\n                  and conditional\n                  <jats:italic>\n                    Camk2a-Cre Chd8\n                    <jats:sup>+\/-<\/jats:sup>\n                  <\/jats:italic>\n                  mice identified shared transcriptional pathology. DE in synaptosomal versus nuclear mRNA identified overlapping DEGs, but also significant differences and exaggerated synaptosomal changes. Building on DE findings implicating glutamatergic neurons, we found\n                  <jats:italic>\n                    Chd8\n                    <jats:sup>+\/-<\/jats:sup>\n                  <\/jats:italic>\n                  mice exhibited altered excitatory neuron spine density and dynamics, decreased GCaMP activity correlation, and sleep perturbation. Thus,\n                  <jats:italic>Chd8<\/jats:italic>\n                  haploinsufficiency causes lasting excitatory neuron dysfunction, perturbs RNA regulation beyond transcription, and impacts neuronal properties, cortical microcircuits, and behavior.\n                <\/jats:p>","DOI":"10.1101\/2025.06.04.657776","type":"posted-content","created":{"date-parts":[[2025,6,5]],"date-time":"2025-06-05T03:30:30Z","timestamp":1749094230000},"source":"Crossref","is-referenced-by-count":2,"title":["Persistent cortical excitatory neuron dysregulation in adult\n                  <i>Chd8<\/i>\n                  haploinsufficient mice"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2505-8367","authenticated-orcid":false,"given":"Cesar P.","family":"Canales","sequence":"first","affiliation":[{"name":"UC Davis Center for Neuroscience, Davis, CA 95618, USA"},{"name":"Department of Psychiatry and Behavioral Sciences, University of California Davis, Sacramento, CA 95817, USA"},{"name":"The M.I.N.D. 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