{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T00:09:17Z","timestamp":1788566957134,"version":"build-2803163510"},"reference-count":93,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T00:00:00Z","timestamp":1730851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with strong genetic heterogeneity and more prevalent in males than females. We and others hypothesize that diminished activity-dependent neural signaling is a common molecular pathway dysregulated in ASD caused by diverse genetic mutations. Brain-derived neurotrophic factor (BDNF) is a key growth factor mediating activity-dependent neural signaling in the brain. A common single nucleotide polymorphism (SNP) in the pro-domain of the human <jats:italic>BDNF<\/jats:italic> gene that leads to a methionine (Met) substitution for valine (Val) at codon 66 (Val66Met) significantly decreases activity-dependent BDNF release without affecting basal BDNF secretion. By using mice with genetic knock-in of this human BDNF methionine (Met) allele, our previous studies have shown differential severity of autism-like social deficits in male and female BDNF<jats:sup>+\/Met<\/jats:sup> mice. Pyramidal neurons are the principal neurons in the prefrontal cortex (PFC), a key brain region for social behaviors. Here, we investigated the impact of diminished activity-dependent BDNF signaling on the intrinsic excitability of pyramidal neurons in the PFC. Surprisingly, diminished activity-dependent BDNF signaling significantly increased the intrinsic excitability of pyramidal neurons in male mice, but not in female mice. Notably, significantly decreased thresholds of action potentials were observed in male BDNF<jats:sup>+\/Met<\/jats:sup> mice, but not in female BDNF<jats:sup>+\/Met<\/jats:sup> mice. Voltage-clamp recordings revealed that the sodium current densities were significantly increased in the pyramidal neurons of male BDNF<jats:sup>+\/Met<\/jats:sup> mice, which were mediated by increased transcriptional level of <jats:italic>Scn2a<\/jats:italic> encoding sodium channel Na<jats:sub>V<\/jats:sub> 1.2. Medium after hyperpolarization (mAHP), another important parameter to determine intrinsic neuronal excitability, is strongly associated with neuronal firing frequency. Further, the amplitudes of mAHP were significantly decreased in male BDNF<jats:sup>+\/Met<\/jats:sup> mice only, which were mediated by the downregulation of <jats:italic>Kcnn2<\/jats:italic> encoding small conductance calcium-activated potassium channel 2 (SK2). This study reveals a sexually dimorphic signature of diminished activity-dependent BDNF signaling on the intrinsic neuronal excitability of pyramidal neurons in the PFC, which provides possible cellular and molecular mechanisms underpinning the sex differences in idiopathic ASD patients and human autism victims who carry BDNF Val66Met SNP.<\/jats:p>","DOI":"10.3389\/fncel.2024.1496930","type":"journal-article","created":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T04:28:15Z","timestamp":1730867295000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["A sexually dimorphic signature of activity-dependent BDNF signaling on the intrinsic excitability of pyramidal neurons in the prefrontal cortex"],"prefix":"10.3389","volume":"18","author":[{"given":"Kaijie","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daoqi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kylee","family":"McDaniel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Webb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel S.","family":"Newton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis S.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luye","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,11,6]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"733","DOI":"10.3389\/fgene.2019.00733","article-title":"Novel gene-based analysis of ASD GWAS: insight into the biological role of associated genes","volume":"10","author":"Alonso-Gonzalez","year":"2019","journal-title":"Front. 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Neurosci."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1152\/physrev.00029.2008","article-title":"Hyperpolarization-activated cation channels: from genes to function","volume":"89","author":"Biel","year":"2009","journal-title":"Physiol. Rev."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1002\/aur.1514","article-title":"Treatment resistant epilepsy in Autism Spectrum disorder: increased risk for females","volume":"9","author":"Blackmon","year":"2016","journal-title":"Autism Res."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.1111\/j.1476-5381.2009.00111.x","article-title":"Neural KCNQ (Kv7) channels","volume":"156","author":"Brown","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/nrn1078","article-title":"Neurotrophins and their receptors: a convergence point for many signalling pathways","volume":"4","author":"Chao","year":"2003","journal-title":"Nat. Rev. Neurosci."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"107266","DOI":"10.1016\/j.nlm.2020.107266","article-title":"The role of intrinsic excitability in the evolution of memory: significance in memory allocation, consolidation, and updating","volume":"173","author":"Chen","year":"2020","journal-title":"Neurobiol. Learn. Mem."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1126\/science.1129663","article-title":"Genetic variant BDNF (Val66Met) polymorphism alters anxiety-related behavior","volume":"314","author":"Chen","year":"2006","journal-title":"Science"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"106107","DOI":"10.1016\/j.nbd.2023.106107","article-title":"HCN channels and absence seizures","volume":"181","author":"Crunelli","year":"2023","journal-title":"Neurobiol. Dis."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/S0006-3223(01)01328-2","article-title":"Anxiety and affective style: role of prefrontal cortex and amygdala","volume":"51","author":"Davidson","year":"2002","journal-title":"Biol. 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Genet."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1113\/jphysiol.2005.086835","article-title":"Kv7\/KCNQ\/M and HCN\/h, but not KCa2\/SK channels, contribute to the somatic medium after-hyperpolarization and excitability control in CA1 hippocampal pyramidal cells","volume":"566","author":"Gu","year":"2005","journal-title":"J. Physiol."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fncel.2011.00001","article-title":"Spiking patterns of neocortical L5 pyramidal neurons in vitro change with temperature","volume":"5","author":"Hedrick","year":"2011","journal-title":"Front. Cell. 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Protoc."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"1963","DOI":"10.1177\/0883073815601501","article-title":"Autism Spectrum disorder and epilepsy: two sides of the same coin?","volume":"30","author":"Jeste","year":"2015","journal-title":"J. Child Neurol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1038\/s41380-020-00995-x","article-title":"FOXP1 negatively regulates intrinsic excitability in D2 striatal projection neurons by promoting inwardly rectifying and leak potassium currents","volume":"26","author":"Khandelwal","year":"2021","journal-title":"Mol. Psychiatry"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s13293-022-00468-6","article-title":"Sex differences in the medial prefrontal cortical glutamate system","volume":"13","author":"Knouse","year":"2022","journal-title":"Biol. Sex Differ."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1038\/nn.4293","article-title":"Serotonin modulates spike probability in the axon initial segment through HCN channels","volume":"19","author":"Ko","year":"2016","journal-title":"Nat. Neurosci."},{"key":"ref41","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1038\/nrn1938","article-title":"The distribution and targeting of neuronal voltage-gated ion channels","volume":"7","author":"Lai","year":"2006","journal-title":"Nat. Rev. Neurosci."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1016\/j.biopsych.2016.05.011","article-title":"Excitation\/inhibition imbalance in animal models of Autism Spectrum disorders","volume":"81","author":"Lee","year":"2017","journal-title":"Biol. Psychiatry"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/0896-6273(92)90135-Z","article-title":"Functional modulation of brain sodium channels by cAMP-dependent phosphorylation","volume":"8","author":"Li","year":"1992","journal-title":"Neuron"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1093\/emboj\/cdg032","article-title":"Absence epilepsy and sinus dysrhythmia in mice lacking the pacemaker channel HCN2","volume":"22","author":"Ludwig","year":"2003","journal-title":"EMBO J."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"1182472","DOI":"10.3389\/fpsyt.2023.1182472","article-title":"Diminished activity-dependent BDNF signaling differentially causes autism-like behavioral deficits in male and female mice","volume":"14","author":"Ma","year":"2023","journal-title":"Front. Psych."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/B978-0-444-63326-2.00002-8","article-title":"Potassium channel genes and benign familial neonatal epilepsy","volume":"213","author":"Maljevic","year":"2014","journal-title":"Prog. Brain Res."},{"key":"ref47","doi-asserted-by":"publisher","first-page":"100442","DOI":"10.1016\/j.xpro.2021.100442","article-title":"Patch-clamp and multi-electrode array electrophysiological analysis in acute mouse brain slices","volume":"2","author":"Manz","year":"2021","journal-title":"STAR Protoc."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1113\/jphysiol.2013.267872","article-title":"Complementary functions of SK and Kv7\/M potassium channels in excitability control and synaptic integration in rat hippocampal dentate granule cells","volume":"592","author":"Mateos-Aparicio","year":"2014","journal-title":"J. Physiol."},{"key":"ref49","doi-asserted-by":"publisher","first-page":"7740","DOI":"10.1523\/JNEUROSCI.6136-09.2010","article-title":"Isolation of somatic Na+ currents by selective inactivation of axonal channels with a voltage prepulse","volume":"30","author":"Milescu","year":"2010","journal-title":"J. Neurosci."},{"key":"ref50","doi-asserted-by":"publisher","DOI":"10.1002\/prot.26643","article-title":"The enigmatic HCN channels: a cellular neurophysiology perspective","author":"Mishra","year":"2023","journal-title":"Proteins"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1016\/j.cell.2017.11.002","article-title":"Combined social and spatial coding in a descending projection from the prefrontal cortex","volume":"171","author":"Murugan","year":"2017","journal-title":"Cell"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1038\/s41401-022-00935-1","article-title":"Channelopathy of small- and intermediate-conductance ca(2+)-activated K(+) channels","volume":"44","author":"Nam","year":"2023","journal-title":"Acta Pharmacol. Sin."},{"key":"ref53","doi-asserted-by":"publisher","first-page":"640","DOI":"10.1038\/ng.2952","article-title":"De novo mutations in HCN1 cause early infantile epileptic encephalopathy","volume":"46","author":"Nava","year":"2014","journal-title":"Nat. Genet."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"916","DOI":"10.1038\/mp.2015.27","article-title":"The BDNF gene Val66Met polymorphism as a modifier of psychiatric disorder susceptibility: progress and controversy","volume":"20","author":"Notaras","year":"2015","journal-title":"Mol. 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Neurosci."},{"key":"ref57","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1684\/epd.2019.1030","article-title":"A novel mutation in KCNQ3-related benign familial neonatal epilepsy: electroclinical features and neurodevelopmental outcome","volume":"21","author":"Piro","year":"2019","journal-title":"Epileptic Disord."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1038\/s41593-018-0110-8","article-title":"Social deficits in Shank3-deficient mouse models of autism are rescued by histone deacetylase (HDAC) inhibition","volume":"21","author":"Qin","year":"2018","journal-title":"Nat Neurosci."},{"key":"ref59","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.isci.2019.06.014","article-title":"Chemogenetic activation of prefrontal cortex in Shank3-deficient mice ameliorates social deficits, NMDAR hypofunction, and Sgk2 downregulation","volume":"17","author":"Qin","year":"2019","journal-title":"iScience"},{"key":"ref60","doi-asserted-by":"publisher","first-page":"6589","DOI":"10.1038\/s41467-021-26972-8","article-title":"Deficiency of autism risk factor ASH1L in prefrontal cortex induces epigenetic aberrations and seizures","volume":"12","author":"Qin","year":"2021","journal-title":"Nat. Commun."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1007\/s11689-009-9012-0","article-title":"A functional polymorphism of the brain derived neurotrophic factor gene and cortical anatomy in autism spectrum disorder","volume":"1","author":"Raznahan","year":"2009","journal-title":"J. Neurodev. Disord."},{"key":"ref62","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.celrep.2018.12.018","article-title":"Augmented reticular thalamic bursting and seizures in Scn1a-Dravet syndrome","volume":"26","author":"Ritter-Makinson","year":"2019","journal-title":"Cell Rep."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1016\/j.tins.2018.03.011","article-title":"Progress in understanding and treating SCN2A-mediated disorders","volume":"41","author":"Sanders","year":"2018","journal-title":"Trends Neurosci."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1111\/j.1528-1167.2011.03069.x","article-title":"Medically refractory epilepsy in autism","volume":"52","author":"Sansa","year":"2011","journal-title":"Epilepsia"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.neuron.2015.03.003","article-title":"Dysfunction of cortical dendritic integration in neuropathic pain reversed by serotoninergic neuromodulation","volume":"86","author":"Santello","year":"2015","journal-title":"Neuron"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1146\/annurev-pharmtox-010919-023356","article-title":"Hyperpolarization-activated cyclic nucleotide-gated channels as drug targets for neurological disorders","volume":"60","author":"Santoro","year":"2020","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1016\/j.cell.2019.12.036","article-title":"Large-scale exome Sequencing study implicates both developmental and functional changes in the neurobiology of Autism","volume":"180","author":"Satterstrom","year":"2020","journal-title":"Cell"},{"key":"ref68","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1002\/ajmg.a.62616","article-title":"Zimmermann-Laband syndrome in monozygotic twins with a mild neurobehavioral phenotype lacking gingival overgrowth-a case report of a novel KCNN3 gene variant","volume":"188","author":"Schwarz","year":"2022","journal-title":"Am. J. Med. Genet. A"},{"key":"ref69","doi-asserted-by":"publisher","first-page":"11817","DOI":"10.1523\/JNEUROSCI.1390-16.2016","article-title":"Considering sex as a biological variable will be valuable for neuroscience research","volume":"36","author":"Shansky","year":"2016","journal-title":"J. Neurosci."},{"key":"ref70","doi-asserted-by":"publisher","first-page":"5311","DOI":"10.1523\/JNEUROSCI.3919-13.2014","article-title":"Conditional deletions of epilepsy-associated KCNQ2 and KCNQ3 channels from cerebral cortex cause differential effects on neuronal excitability","volume":"34","author":"Soh","year":"2014","journal-title":"J. Neurosci."},{"key":"ref71","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1002\/humu.22500","article-title":"Novel KCNQ2 and KCNQ3 mutations in a large cohort of families with benign neonatal epilepsy: first evidence for an altered channel regulation by syntaxin-1A","volume":"35","author":"Soldovieri","year":"2014","journal-title":"Hum. Mutat."},{"key":"ref72","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1038\/mp.2017.144","article-title":"BDNF at the synapse: why location matters","volume":"22","author":"Song","year":"2017","journal-title":"Mol. 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