{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T19:34:32Z","timestamp":1790192072775,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T00:00:00Z","timestamp":1750118400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012247","name":"Program of Shanghai Academic Research Leader","doi-asserted-by":"publisher","award":["21XD1400100"],"award-info":[{"award-number":["21XD1400100"]}],"id":[{"id":"10.13039\/501100012247","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2020M681160"],"award-info":[{"award-number":["2020M681160"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32100930"],"award-info":[{"award-number":["32100930"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32130044"],"award-info":[{"award-number":["32130044"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271499"],"award-info":[{"award-number":["82271499"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["T2241002"],"award-info":[{"award-number":["T2241002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Focal cortical dysplasia type II (FCDII) is one of the most common causes of refractory epilepsy. Hyperactivated mechanistic target of rapamycin (mTOR) pathway resulting from genetic mutations underlies FCDII, but it remains controversial and poorly understood whether the dysmorphic neurons play a role in cortical hyperexcitability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Here, we performed whole\u2010cell recordings from dysmorphic neurons and nearby normal\u2010appearing neurons in an FCDII mouse model with a\n                      <jats:italic>PIK3CA<\/jats:italic>\n                      mutation to examine intrinsic excitability and excitatory\/inhibitory (E\/I) synaptic inputs. To decipher the net effects of intrinsic excitability and synaptic transmission, we delivered extracellular electric stimulation to evoke action potentials (APs) and obtained the current threshold. To explore the underlying mechanisms, immunofluorescent staining was used to analyze the neuronal morphology, and rapamycin was injected into mice to suppress the activity of mTOR pathway. \u03b3\u2010Aminobutyric acid type B (GABA\n                      <jats:sub>B<\/jats:sub>\n                      ) receptor agonist (baclofen) was applied to modulate the excitability of dysmorphic neurons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We found that dysmorphic neurons exhibited ultralow intrinsic excitability but enhanced excitatory synaptic inputs. Additionally, lower threshold intensity was required for them to evoke APs. This hyperexcitability could be attributable to mTOR\u2010dependent increased dendritic complexity and spine density, as postnatal rapamycin application rescued these changes. Importantly, we found that activation of presynaptic GABA\n                      <jats:sub>B<\/jats:sub>\n                      receptors could specifically reduce excitatory synaptic inputs and normalize the E\/I dysfunction, and thus decrease the excitability of dysmorphic neurons.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      Together, these findings indicate that excessive excitatory synaptic inputs prevail over reduced intrinsic excitability in dysmorphic neurons, leading to hyperexcitability in FCDII. Furthermore, they strongly suggest GABA\n                      <jats:sub>B<\/jats:sub>\n                      receptors as a potential therapeutic target for FCDII.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.18498","type":"journal-article","created":{"date-parts":[[2025,6,17]],"date-time":"2025-06-17T10:53:33Z","timestamp":1750157613000},"page":"4006-4022","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Dysmorphic neurons with ultralow intrinsic excitability are paradoxically hyperexcitable in neural network in a mouse model of focal cortical dysplasia type\n                    <scp>II<\/scp>"],"prefix":"10.1111","volume":"66","author":[{"given":"Shuyang","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurology, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kexian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quansheng","family":"He","sequence":"additional","affiliation":[{"name":"Institutes for Translational Brain Research, State Key Laboratory of Brain Function and Disorders, Ministry of Education Frontiers Center for Brain Science Fudan University  Shanghai China"},{"name":"Ministry of Education Innovative Center for New Drug Development of Immune Inflammatory Diseases Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongkun","family":"Yang","sequence":"additional","affiliation":[{"name":"Institutes for Translational Brain Research, State Key Laboratory of Brain Function and Disorders, Ministry of Education Frontiers Center for Brain Science Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuling","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousheng","family":"Shu","sequence":"additional","affiliation":[{"name":"Institutes for Translational Brain Research, State Key Laboratory of Brain Function and Disorders, Ministry of Education Frontiers Center for Brain Science Fudan University  Shanghai China"},{"name":"Ministry of Education Innovative Center for New Drug Development of Immune Inflammatory Diseases Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5135-4210","authenticated-orcid":false,"given":"Jing","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Neurology, Zhongshan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,17]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1703784"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.16899"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-019-02061-5"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-024-01634-2"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51286"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)32596-0"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25403"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/aww192"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abc1492"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26149"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-020-02086-y"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2329"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv045"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab376"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.12703"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathmechdis-012418-012927"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02777.x"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.12.012"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1999.00467.x"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa387"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.111574"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI99384"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-022-00828-7"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddz123"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31419-2"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-021-01122-6"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.107808"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/brainsci12040419"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11753"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab390"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.91010"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2021.772847"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-019-0427-6"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.02.004"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1190287"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aaw1888"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abm7466"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.628541"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2020.11.001"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/nlz096"},{"key":"e_1_2_12_42_1","first-page":"399","volume-title":"Handbook 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