{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T13:52:14Z","timestamp":1770817934722,"version":"3.50.1"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Neuroscience","award":["24-8"],"award-info":[{"award-number":["24-8"]}]},{"name":"National Institute of Neuroscience","award":["24-12"],"award-info":[{"award-number":["24-12"]}]},{"name":"National Institute of Neuroscience","award":["25-3"],"award-info":[{"award-number":["25-3"]}]},{"name":"National Institute of Neuroscience","award":["30-7"],"award-info":[{"award-number":["30-7"]}]},{"name":"National Institute of Neuroscience","award":["27-6"],"award-info":[{"award-number":["27-6"]}]},{"name":"Japanese ministry of Health, Labor and Welfare","award":["H23-001"],"award-info":[{"award-number":["H23-001"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["acta neuropathol commun"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The Ihara epileptic rat (IER) is a mutant model with limbic-like seizures whose pathology and causative gene remain elusive. In this report, via linkage analysis, we identified Down syndrome cell adhesion molecule-like 1(<jats:italic>Dscaml1<\/jats:italic>) as the responsible gene for IER. A single base mutation in <jats:italic>Dscaml1<\/jats:italic> causes abnormal splicing, leading to lack of DSCAML1. IERs have enhanced seizure susceptibility and accelerated kindling establishment. Furthermore, GABAergic neurons are severely reduced in the entorhinal cortex (ECx) of these animals. Voltage-sensitive dye imaging that directly presents the excitation status of brain slices revealed abnormally persistent excitability in IER ECx. This suggests that reduced GABAergic neurons may cause weak sustained entorhinal cortex activations, leading to natural kindling\u00a0via\u00a0the perforant path that could cause dentate gyrus hypertrophy and epileptogenesis. Furthermore, we identified a single nucleotide substitution in a human epilepsy that would result in one amino acid change in DSCAML1 (A2105T mutation). The mutant DSCAML1<jats:sup>A2105T<\/jats:sup> protein is not presented on the cell surface, losing its homophilic cell adhesion ability. We generated knock-in mice (<jats:italic>Dscaml1<\/jats:italic><jats:sup><jats:italic>A2105T<\/jats:italic><\/jats:sup>) carrying the corresponding mutation and observed reduced GABAergic neurons in the ECx as well as spike-and-wave electrocorticogram. We conclude that DSCAML1 is required for GABAergic neuron placement in the ECx and suppression of seizure susceptibility in rodents. Our findings suggest that mutations in DSCAML1 may affect seizure susceptibility in humans.<\/jats:p>","DOI":"10.1186\/s40478-020-01082-6","type":"journal-article","created":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T11:03:07Z","timestamp":1606734187000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Down syndrome cell adhesion molecule like-1 (DSCAML1) links the GABA system and seizure susceptibility"],"prefix":"10.1186","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0638-2850","authenticated-orcid":false,"given":"Yoneko","family":"Hayase","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeru","family":"Amano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Hashizume","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takashi","family":"Tominaga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Miyamoto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukie","family":"Kanno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko","family":"Ueno-Inoue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayoshi","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayumi","family":"Yamada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigehiro","family":"Ogata","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shabeesh","family":"Balan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Hayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiki","family":"Miura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kentaro","family":"Tokudome","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukihiro","family":"Ohno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takuma","family":"Nishijo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihiko","family":"Momiyama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuchio","family":"Yanagawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiko","family":"Takizawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomoji","family":"Mashimo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadao","family":"Serikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akihiro","family":"Sekine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eiji","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eri","family":"Takeshita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeo","family":"Yoshikawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chikako","family":"Waga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ken","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-ichi","family":"Goto","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoichi","family":"Nabeshima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuo","family":"Ihara","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiro","family":"Yamakawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichiro","family":"Taya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikio","family":"Hoshino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,11,30]]},"reference":[{"key":"1082_CR1","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1038\/nature12439","volume":"501","author":"Epi4K Consortium; Epilepsy Phenome\/Genome Project","year":"2013","unstructured":"Epi4K Consortium; Epilepsy Phenome\/Genome Project (2013) De novo mutations in epileptic encephalopathies. Nature 501:217\u2013221. https:\/\/doi.org\/10.1038\/nature12439","journal-title":"Nature"},{"key":"1082_CR2","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.ajhg.2014.08.013","volume":"100","author":"EuroEPINOMICS Consortium, Epilepsy Phenome\/Genome Project and Epi4K Consortium","year":"2017","unstructured":"EuroEPINOMICS Consortium, Epilepsy Phenome\/Genome Project and Epi4K Consortium (2017) De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies. Am J Hum Genet 100:179. https:\/\/doi.org\/10.1016\/j.ajhg.2014.08.013","journal-title":"Am J Hum Genet"},{"key":"1082_CR3","first-page":"329","volume":"149","author":"S Amano","year":"1996","unstructured":"Amano S, Ihara N, Uemura S, Yokoyama M, Ikeda M, Serikawa T et al (1996) Development of a novel rat mutant with spontaneous limbic-like seizures. Am J Pathol 149:329\u2013333","journal-title":"Am J Pathol"},{"key":"1082_CR4","first-page":"317","volume":"47","author":"S Amano","year":"1997","unstructured":"Amano S, Yokoyama M, Torii R, Fukuoka J, Tanaka K, Ihara N et al (1997) High performance seizure-monitoring system using a vibration sensor and videotape recording: behavioral analysis of genetically epileptic rats. Lab Anim Sci 47:317\u2013320","journal-title":"Lab Anim Sci"},{"key":"1082_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/s0006-8993(01)01994-1","volume":"901","author":"A Tsuji","year":"2001","unstructured":"Tsuji A, Amano S, Yokoyama M, Fukuoka J, Hayase Y, Matsuda M (2001) Neuronal microdysgenesis and acquired lesions of the hippocampal formation connected with seizure activities in Ihara epileptic rat. Brain Res 901:1\u201311. https:\/\/doi.org\/10.1016\/s0006-8993(01)01994-1","journal-title":"Brain Res"},{"key":"1082_CR6","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1111\/j.1528-1167.2006.00370.x","volume":"47","author":"Y Okaichi","year":"2006","unstructured":"Okaichi Y, Amano S, Ihara N, Hayase Y, Tazumi T, Okaichi H (2006) Open-field behaviors and water-maze learning in the F substrain of Ihara epileptic rats. Epilepsia 47:55\u201363. https:\/\/doi.org\/10.1111\/j.1528-1167.2006.00370.x","journal-title":"Epilepsia"},{"key":"1082_CR7","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1006\/bbrc.2001.5214","volume":"285","author":"KL Agarwala","year":"2001","unstructured":"Agarwala KL, Ganesh S, Tsutsumi Y, Suzuki T, Amano K, Yamakawa K (2001) Cloning and functional characterization of DSCAML1, a novel DSCAM-like cell adhesion molecule that mediates homophilic intercellular adhesion. Biochem Biophys Res Commun 285:760\u2013772. https:\/\/doi.org\/10.1006\/bbrc.2001.5214","journal-title":"Biochem Biophys Res Commun"},{"key":"1082_CR8","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1038\/nature06514","volume":"451","author":"PG Fuerst","year":"2008","unstructured":"Fuerst PG, Koizumi A, Masland RH, Burgess RW (2008) Neurite arborization and mosaic spacing in the mouse retina require DSCAM. Nature 451:470\u2013474. https:\/\/doi.org\/10.1038\/nature06514","journal-title":"Nature"},{"key":"1082_CR9","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1016\/j.cell.2010.10.009","volume":"143","author":"SL Zipursky","year":"2010","unstructured":"Zipursky SL, Sanes JR (2010) Chemoaffinity revisited: Dscams, Protocadherins, and Neural circuit assembly. Cell 143:343\u2013353. https:\/\/doi.org\/10.1016\/j.cell.2010.10.009","journal-title":"Cell"},{"key":"1082_CR10","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1016\/j.neuron.2009.09.027","volume":"64","author":"PG Fuerst","year":"2009","unstructured":"Fuerst PG, Bruce F, Tian M, Wei W, Elstrott J, Feller MB et al (2009) DSCAM and DSCAML1 function in self-avoidance in multiple cell types in the developing mouse retina. Neuron 64:484\u2013497. https:\/\/doi.org\/10.1016\/j.neuron.2009.09.027","journal-title":"Neuron"},{"key":"1082_CR11","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.neulet.2013.09.052","volume":"555","author":"S Cui","year":"2013","unstructured":"Cui S, Lao L, Duan J, Jin G, Hou X (2013) Tyrosine phosphorylation is essential for DSCAML1 to promote dendrite arborization of mouse cortical neurons. Neurosci Lett 555:193\u2013197. https:\/\/doi.org\/10.1016\/j.neulet.2013.09.052","journal-title":"Neurosci Lett"},{"key":"1082_CR12","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1002\/cne.10905","volume":"467","author":"N Tamamaki","year":"2003","unstructured":"Tamamaki N, Yanagawa Y, Tomioka R, Miyazaki J, Obata K, Kaneko T (2003) Green fluorescent protein expression and colocalization with calretinin, parvalbumin, and somatostatin in the GAD67-GFP knock-in mouse. J Comp Neurol 467:60\u201379. https:\/\/doi.org\/10.1002\/cne.10905","journal-title":"J Comp Neurol"},{"key":"1082_CR13","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1038\/s42003-018-0099-2","volume":"1","author":"I Ogiwara","year":"2018","unstructured":"Ogiwara I, Miyamoto H, Tatsukawa T, Yamagata T, Nakayama T, Atapour N et al (2018) Nav12 haplodeficiency in excitatory neurons causes absence-like seizures in mice. Commun Biol 1:96. https:\/\/doi.org\/10.1038\/s42003-018-0099-2","journal-title":"Commun Biol"},{"key":"1082_CR14","doi-asserted-by":"publisher","first-page":"27402","DOI":"10.1038\/srep27420","volume":"6","author":"K Tokudome","year":"2016","unstructured":"Tokudome K, Okumura T, Shimizu S, Mashimo T, Takizawa A, Serikawa T et al (2016) Synaptic vesicle glycoprotein 2A (SV2A) regulates kindling epileptogenesis via GABAergic neurotransmission. Sci Rep 6:27402. https:\/\/doi.org\/10.1038\/srep27420","journal-title":"Sci Rep"},{"key":"1082_CR15","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.neuroscience.2014.01.010","volume":"263","author":"A Sato","year":"2014","unstructured":"Sato A, Ssaoka T, Nishijo T, Momiyama T (2014) GABAergic synaptic transmission onto striatal cholinergic interneurons in dopamine D2 receptor knock-out mouse. Neuroscience 263:138\u2013147. https:\/\/doi.org\/10.1016\/j.neuroscience.2014.01.010","journal-title":"Neuroscience"},{"key":"1082_CR16","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1152\/jn.00856.2012","volume":"110","author":"T Tominaga","year":"2013","unstructured":"Tominaga T, Tominaga Y (2013) A new nonscanning confocal microscopy module for functional voltage-sensitive dye and Ca2+ imaging of neuronal circuit activity. J Neurophysiol 110:553\u2013561. https:\/\/doi.org\/10.1152\/jn.00856.2012","journal-title":"J Neurophysiol"},{"key":"1082_CR17","doi-asserted-by":"publisher","first-page":"389","DOI":"10.3389\/fncel.2018.00389","volume":"12","author":"Y Tominaga","year":"2018","unstructured":"Tominaga Y, Taketoshi M, Tominaga T (2018) Overall assay of neuronal signal propagation pattern with long-term potentiation (LTP) in hippocampal slices from the CA1 area with fast voltage-sensitive dye imaging. Front Cell Neurosci 12:389. https:\/\/doi.org\/10.3389\/fncel.2018.00389","journal-title":"Front Cell Neurosci"},{"key":"1082_CR18","doi-asserted-by":"publisher","first-page":"20","DOI":"10.3389\/fncel.2019.00020","volume":"13","author":"R Kajiwara","year":"2019","unstructured":"Kajiwara R, Tominaga Y, Tominaga T (2019) Network plasticity involved in the spread of neural activity within the rhinal cortices as revealed by voltage-sensitive dye imaging in mouse brain slices. Front Cell Neurosci 13:20. https:\/\/doi.org\/10.3389\/fncel.2019.00020","journal-title":"Front Cell Neurosci"},{"key":"1082_CR19","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/BF00431248","volume":"3","author":"T Serikawa","year":"1992","unstructured":"Serikawa T, Montagutelli X, Simon-Chazottes D, Gu\u00e9net JL (1992) Polymorphisms revealed by PCR with single, short-sized, arbitrary primers are reliable markers for mouse and rat gene mapping. Mamm Genome 3:65\u201372. https:\/\/doi.org\/10.1007\/BF00431248","journal-title":"Mamm Genome"},{"key":"1082_CR20","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/s003350010263","volume":"12","author":"M Yokoyama","year":"2001","unstructured":"Yokoyama M, Amano S, Tsuji A, Sasahara M, Serikawa T, Ihara N et al (2001) Genetic analysis of cataract in Ihara epileptic rat. Mamm Genome 12:207\u2013211. https:\/\/doi.org\/10.1007\/s003350010263","journal-title":"Mamm Genome"},{"key":"1082_CR21","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1007\/s00335-001-1016-3","volume":"12","author":"KF Manly","year":"2001","unstructured":"Manly KF, Cudmore RH Jr, Meer JM (2001) MAP manager QTX, crossplatform software for genetic mapping. Mamm Genome 12:930\u2013932. https:\/\/doi.org\/10.1007\/s00335-001-1016-3","journal-title":"Mamm Genome"},{"key":"1082_CR22","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1002\/ajmg.b.30638","volume":"147B","author":"K Takano","year":"2008","unstructured":"Takano K, Nakagawa E, Inoue K, Kamada F, Kure S, Goto Y (2008) A loss-of-function mutation in the FTSJ1 gene causes nonsyndromic X-linked mental retardation in a Japanese family. Am J Med Genet B Neuropsychiatr Genet 147B:479\u2013484. https:\/\/doi.org\/10.1002\/ajmg.b.30638","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"key":"1082_CR23","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1016\/j.braindev.2011.12.010","volume":"34","author":"E Takeshita","year":"2012","unstructured":"Takeshita E, Nakagawa E, Nakatani K, Sasaki M, Goto Y (2012) Novel AGTR2 missense mutation in a Japanese boy with severe mental retardation, pervasive developmental disorder, and epilepsy. Brain Dev 34:776\u2013779. https:\/\/doi.org\/10.1016\/j.braindev.2011.12.010","journal-title":"Brain Dev"},{"key":"1082_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ydbio.2016.07.017","volume":"418","author":"M Hashimoto","year":"2016","unstructured":"Hashimoto M, Yamashita Y, Takemoto T (2016) Electroporation of Cas9 protein\/sgRNA into early pronuclear zygotes generates non-mosaic mutants in the mouse. Dev Biol 418:1\u20139. https:\/\/doi.org\/10.1016\/j.ydbio.2016.07.017","journal-title":"Dev Biol"},{"key":"1082_CR25","doi-asserted-by":"publisher","first-page":"2166","DOI":"10.1016\/j.celrep.2014.11.045","volume":"9","author":"K Hori","year":"2014","unstructured":"Hori K, Nagai T, Shan W, Sakamoto A, Taya S, Hashimoto R (2014) Cytoskeletal regulation by AUTS2 in neuronal migration and neuritogenesis. Cell Rep 9:2166\u20132179. https:\/\/doi.org\/10.1016\/j.celrep.2014.11.045","journal-title":"Cell Rep"},{"key":"1082_CR26","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1523\/JNEUROSCI.1545-17.2017","volume":"38","author":"T Owa","year":"2018","unstructured":"Owa T, Taya S, Miyashita S, Yamashita M, Adachi T, Yamada K (2018) Meis1 coordinates cerebellar granule cell development by regulating Pax6 transcription, BMP signaling and Atoh1 degradation. J Neurosci 38:1277\u20131294. https:\/\/doi.org\/10.1523\/JNEUROSCI.1545-17.2017","journal-title":"J Neurosci"},{"key":"1082_CR27","doi-asserted-by":"publisher","first-page":"1693","DOI":"10.1126\/sciadv.aba1693","volume":"6","author":"N Arimura","year":"2020","unstructured":"Arimura N, Okada M, Taya S, Dewa KI, Tsuzuki A, Uetake H (2020) DSCAM regulates delamination of neurons in the developing midbrain. Sci Adv 6:1693. https:\/\/doi.org\/10.1126\/sciadv.aba1693","journal-title":"Sci Adv"},{"key":"1082_CR28","doi-asserted-by":"publisher","first-page":"3465","DOI":"10.1083\/jcb.109.6.3465","volume":"109","author":"JA Pizzey","year":"1989","unstructured":"Pizzey JA, Rowett LH, Barton CH, Dickson G, Walsh FS (1989) Intercellular adhesion mediated by human muscle neural cell adhesion molecule: effects of alternative exon use. J Cell Biol 109:3465\u20133476. https:\/\/doi.org\/10.1083\/jcb.109.6.3465","journal-title":"J Cell Biol"},{"key":"1082_CR29","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1083\/jcb.118.4.937","volume":"118","author":"Y Rao","year":"1992","unstructured":"Rao Y, Wu XF, Gariepy J, Rutishauser U, Siu CH (1992) Identification of a peptide sequence involved in homophilic binding in the neural cell adhesion molecule NCAM. J Cell Biol 118:937\u2013949. https:\/\/doi.org\/10.1083\/jcb.118.4.937","journal-title":"J Cell Biol"},{"key":"1082_CR30","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1007\/BF01990433","volume":"39","author":"N Ihara","year":"1983","unstructured":"Ihara N (1983) A new strain of rat with an inherited cataract. Experientia 39:909\u2013911. https:\/\/doi.org\/10.1007\/BF01990433","journal-title":"Experientia"},{"key":"1082_CR31","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1203\/00006450-200103000-00004","volume":"49","author":"GL Holmes","year":"2001","unstructured":"Holmes GL, Ben-Ari Y (2001) The neurobiology and consequences of epilepsy in the developing brain. Pediatr Res 49:320\u2013325. https:\/\/doi.org\/10.1203\/00006450-200103000-00004","journal-title":"Pediatr Res"},{"key":"1082_CR32","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/0013-4694(72)90177-0","volume":"32","author":"RJ Racine","year":"1972","unstructured":"Racine RJ (1972) Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol 32:281\u2013294. https:\/\/doi.org\/10.1016\/0013-4694(72)90177-0","journal-title":"Electroencephalogr Clin Neurophysiol"},{"key":"1082_CR33","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1016\/s0006-8993(99)01505-x","volume":"834","author":"S Amano","year":"1999","unstructured":"Amano S, Ikeda M, Uemura S, Fukuoka J, Tsuji A, Sasahara M et al (1999) Mossy fiber sprouting in the dentate gyrus in a newly developed epileptic mutant, Ihara epileptic rat. Brain Res 834:214\u2013218. https:\/\/doi.org\/10.1016\/s0006-8993(99)01505-x","journal-title":"Brain Res"},{"key":"1082_CR34","unstructured":"Cajal SRY (1893) Estructura del asta de Ammon y fascia dentata. Establecimiento Tipogr\u00e1fico de Portanet"},{"key":"1082_CR35","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1002\/cne.901690306","volume":"169","author":"O Steward","year":"1976","unstructured":"Steward O, Scoville SA (1976) Cells of origin of entorhinal cortical afferents to the hippocampus and fascia dentata of the rat. J Comp Neurol 169:347\u2013370. https:\/\/doi.org\/10.1002\/cne.901690306","journal-title":"J Comp Neurol"},{"key":"1082_CR36","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1038\/nrm4063","volume":"16","author":"S Lykke-Andersen","year":"2015","unstructured":"Lykke-Andersen S, Jensen TH (2015) Nonsense-mediated mRNA decay: an intricate machinery that shapes transcriptomes. Nat Rev Mol Cell Biol 16:665\u2013677. https:\/\/doi.org\/10.1038\/nrm4063","journal-title":"Nat Rev Mol Cell Biol"},{"key":"1082_CR37","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1038\/nrg1327","volume":"5","author":"F Pagani","year":"2004","unstructured":"Pagani F, Baralle FE (2004) Genomic variants in exons and introns: identifying the splicing spoilers. Nat Rev Genet 5:389\u2013396. https:\/\/doi.org\/10.1038\/nrg1327","journal-title":"Nat Rev Genet"},{"key":"1082_CR38","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1038\/35097509","volume":"2","author":"O Marin","year":"2001","unstructured":"Marin O, Rubenstein JL (2001) A long, remarkable journey: tangential migration in the telencephalon. Nat Rev Neurosci 2:780\u2013790. https:\/\/doi.org\/10.1038\/35097509","journal-title":"Nat Rev Neurosci"},{"key":"1082_CR39","doi-asserted-by":"publisher","first-page":"1582","DOI":"10.1523\/JNEUROSCI.4515-09.2010","volume":"30","author":"G Miyoshi","year":"2010","unstructured":"Miyoshi G, Hjerling-Leffler J, Karayannis T, Sousa VH, Butt SJ, Battiste J et al (2010) Genetic fate mapping reveals that the caudal ganglionic eminence produces a large and diverse population of superficial cortical interneurons. J Neurosci 30:1582\u20131594. https:\/\/doi.org\/10.1523\/JNEUROSCI.4515-09.2010","journal-title":"J Neurosci"},{"key":"1082_CR40","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pneurobio.2004.03.009","volume":"73","author":"K Morimoto","year":"2004","unstructured":"Morimoto K, Fahnestock M, Racine RJ (2004) Kindling and status epilepticus models of epilepsy; rewiring the brain. Prog Neurobiol 73:1\u201360. https:\/\/doi.org\/10.1016\/j.pneurobio.2004.03.009","journal-title":"Prog Neurobiol"},{"key":"1082_CR41","doi-asserted-by":"publisher","first-page":"448","DOI":"10.3390\/cells8050448","volume":"8","author":"PA Kipnis","year":"2019","unstructured":"Kipnis PA, Sullivan BJ, Kadam SD (2019) Sex-Dependent signaling pathways underlying seizure susceptibility and the role of chloride cotransporters. Cells 8:448. https:\/\/doi.org\/10.3390\/cells8050448","journal-title":"Cells"}],"container-title":["Acta Neuropathologica Communications"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-020-01082-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s40478-020-01082-6\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s40478-020-01082-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T12:18:15Z","timestamp":1606738695000},"score":1,"resource":{"primary":{"URL":"https:\/\/actaneurocomms.biomedcentral.com\/articles\/10.1186\/s40478-020-01082-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,30]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1082"],"URL":"https:\/\/doi.org\/10.1186\/s40478-020-01082-6","relation":{},"ISSN":["2051-5960"],"issn-type":[{"value":"2051-5960","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,30]]},"assertion":[{"value":"13 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 November 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 November 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The blood samples of the patients and families were obtained from the \u201cDepository of the patients with epilepsy and intellectual disability\u201d of NCNP from the approved project \u201cResearch and utilization of biobank of hereditary, developmental disorder\u201d by the Ethical Committee of NCNP (#XXXX-115, A2014-081). In this project, all participants provided consent. All animal experiments were approved by the Animal Care and Use Committee of the National Institute of Neuroscience, Japan (Project #2008005). All VSD imaging of the rat brain slices were performed according to protocols approved by the Animal Care and Use Committee of Tokushima-Bunri University.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"206"}}