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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2025,11,25]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">SCN2A<\/jats:italic>\n                    is a high-confidence risk gene for autism spectrum disorder. Loss-of-function mutations in\n                    <jats:italic toggle=\"yes\">Scn2a<\/jats:italic>\n                    reduce dendritic excitability in neocortical pyramidal cells. However, the impact of\n                    <jats:italic toggle=\"yes\">Scn2a<\/jats:italic>\n                    haploinsufficiency on dendritic signaling in vivo, particularly during behavior, is unknown. In this study, we used two-photon microscopy to image dendritic calcium transients in deep layer pyramidal cells in the mouse medial frontal cortex.\n                    <jats:italic toggle=\"yes\">\n                      Scn2a\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice had diminished coupling between apical and proximal dendritic compartments. Pyramidal tract neurons had abnormal event rates, while intratelencephalic neurons had compartment-specific alterations indicative of diminished dendritic integration. In a matching pennies task,\n                    <jats:italic toggle=\"yes\">\n                      Scn2a\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice were inflexible in the face of changing competitive pressure. Apical dendritic tuft in intratelencephalic neurons typically encoded reward and strategy, but these task-specific representations were altered in\n                    <jats:italic toggle=\"yes\">\n                      Scn2a\n                      <jats:sup>+\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice. Collectively, the findings demonstrate that\n                    <jats:italic toggle=\"yes\">Scn2a<\/jats:italic>\n                    haploinsufficiency weakens dendritic integration in vivo and disrupts dendritic encoding of task variables during flexible decision-making.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2508836122","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T16:21:33Z","timestamp":1763655693000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":4,"title":["Autism-associated\n                    <i>Scn2a<\/i>\n                    haploinsufficiency disrupts in vivo dendritic signaling and impairs flexible decision-making"],"prefix":"10.1073","volume":"122","author":[{"given":"Hao","family":"Wu","sequence":"first","affiliation":[{"name":"Meinig School of Biomedical Engineering, Cornell University","place":["Ithaca"]},{"name":"Interdepartmental Neuroscience Program, Yale 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