{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:24:33Z","timestamp":1787016273189,"version":"build-2736575974"},"reference-count":60,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,1,29]],"date-time":"2023-01-29T00:00:00Z","timestamp":1674950400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01\/R56 MH100510"],"award-info":[{"award-number":["R01\/R56 MH100510"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["P2ZHP3_168621"],"award-info":[{"award-number":["P2ZHP3_168621"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["P400PB_180785"],"award-info":[{"award-number":["P400PB_180785"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Patients with Fragile X syndrome, the leading monogenetic cause of autism, suffer from impairments related to the prefrontal cortex, including working memory and attention. Synaptic inputs to the distal dendrites of layer 5 pyramidal neurons in the prefrontal cortex have a weak influence on the somatic membrane potential. To overcome this filtering, distal inputs are transformed into local dendritic Na\n                      <jats:sup>+<\/jats:sup>\n                      spikes, which propagate to the soma and trigger action potential output. Layer 5 extratelencephalic (ET) prefrontal cortex (PFC) neurons project to the brainstem and various thalamic nuclei and are therefore well positioned to integrate task\u2010relevant sensory signals and guide motor actions. We used current clamp and outside\u2010out patch clamp recording to investigate dendritic spike generation in ET neurons from male wild\u2010type and\n                      <jats:italic>Fmr1<\/jats:italic>\n                      knockout (FX) mice. The threshold for dendritic spikes was more depolarized in FX neurons compared to wild\u2010type. Analysis of voltage responses to simulated\n                      <jats:italic>in vivo<\/jats:italic>\n                      \u2018noisy\u2019 current injections showed that a larger dendritic input stimulus was required to elicit dendritic spikes in FX ET dendrites compared to wild\u2010type. Patch clamp recordings revealed that the dendritic Na\n                      <jats:sup>+<\/jats:sup>\n                      conductance was significantly smaller in FX ET dendrites. Taken together, our results suggest that the generation of Na\n                      <jats:sup>+<\/jats:sup>\n                      \u2010dependent dendritic spikes is impaired in ET neurons of the PFC in FX mice. Considering our prior findings that somatic D\u2010type K\n                      <jats:sup>+<\/jats:sup>\n                      and dendritic hyperpolarization\u2010activated cyclic nucleotide\u2010gated\u2010channel function is reduced in ET neurons, we suggest that dendritic integration by PFC circuits is fundamentally altered in Fragile X syndrome.\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15418-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            Dendritic spike threshold is depolarized in layer 5 prefrontal cortex neurons in\n                            <jats:italic>Fmr1<\/jats:italic>\n                            knockout (FX) mice.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Simultaneous somatic and dendritic recording with white noise current injections revealed that larger dendritic stimuli were required to elicit dendritic spikes in FX extratelencephalic (ET) neurons.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Outside\u2010out patch clamp recording revealed that dendritic sodium conductance density was lower in FX ET neurons.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp283311","type":"journal-article","created":{"date-parts":[[2023,1,10]],"date-time":"2023-01-10T05:24:59Z","timestamp":1673328299000},"page":"831-845","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Impaired dendritic spike generation in the Fragile X prefrontal cortex is due to loss of dendritic sodium channels"],"prefix":"10.1113","volume":"601","author":[{"given":"Federico","family":"Brandalise","sequence":"first","affiliation":[{"name":"Center for Learning and Memory University of Texas at Austin  Austin TX USA"},{"name":"Department of Neuroscience University of Texas at Austin  Austin TX USA"},{"name":"Department of Biosciences University of Milan  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian 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