{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T12:18:55Z","timestamp":1778933935348,"version":"3.51.4"},"reference-count":84,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T00:00:00Z","timestamp":1584316800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T00:00:00Z","timestamp":1584316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000065","name":"U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R15NS112964"],"award-info":[{"award-number":["R15NS112964"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007249","name":"University of Minnesota","doi-asserted-by":"publisher","award":["Faculty start-up fund"],"award-info":[{"award-number":["Faculty start-up fund"]}],"id":[{"id":"10.13039\/100007249","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neuropsychopharmacol."],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Autism spectrum disorder (ASD) encompasses wide-ranging neuropsychiatric symptoms with unclear etiology. Although the cerebellum is a key region implicated in ASD, it remains elusive how the cerebellar circuitry is altered and whether the cerebellum can serve as a therapeutic target to rectify the phenotype of idiopathic ASD with polygenic abnormalities. Using a syndromic ASD model, e.g., Black and Tan BRachyury T<jats:sup>+<\/jats:sup>Itpr3<jats:sup>tf<\/jats:sup>\/J (BTBR) mice, we revealed that increased excitability of presynaptic interneurons (INs) and decreased intrinsic excitability of postsynaptic Purkinje neurons (PNs) resulted in low PN firing rates in the cerebellum. Knowing that downregulation of Kv1.2 potassium channel in the IN nerve terminals likely augmented their excitability and GABA release, we applied a positive Kv1.2 modulator to mitigate the presynaptic over-inhibition and social impairment of BTBR mice. Selective restoration of the PN activity by a new chemogenetic approach alleviated core ASD-like behaviors of the BTBR strain. These findings highlight complex mechanisms converging onto the cerebellar dysfunction in the phenotypic model and provide effective strategies for potential therapies of ASD.<\/jats:p>","DOI":"10.1038\/s41386-020-0656-5","type":"journal-article","created":{"date-parts":[[2020,3,16]],"date-time":"2020-03-16T18:03:41Z","timestamp":1584381821000},"page":"1159-1170","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Targeting inhibitory cerebellar circuitry to alleviate behavioral deficits in a mouse model for studying idiopathic autism"],"prefix":"10.1038","volume":"45","author":[{"given":"Owen Y.","family":"Chao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ezequiel","family":"Marron Fernandez de Velasco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salil Saurav","family":"Pathak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Swati","family":"Maitra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Duvick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5179-9540","authenticated-orcid":false,"given":"Kevin","family":"Wickman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry T.","family":"Orr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirokazu","family":"Hirai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1491-8106","authenticated-orcid":false,"given":"Yi-Mei","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,3,16]]},"reference":[{"key":"656_CR1","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0140-6736(13)61539-1","volume":"383","author":"MC Lai","year":"2014","unstructured":"Lai MC, Lombardo MV, Baron-Cohen S. Autism. Lancet 2014;383:896\u2013910.","journal-title":"Lancet"},{"key":"656_CR2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.ss6706a1","volume":"67","author":"J Baio","year":"2018","unstructured":"Baio J, Wiggins L, Christensen DL, Maenner MJ, Daniels J, Warren Z, et al. Prevalence of autism spectrum disorder among children aged 8 years\u2014autism and developmental disabilities monitoring network, 11 sites, United States, 2014. MMWR Surveill Summ. 2018;67:1\u201323.","journal-title":"MMWR Surveill Summ"},{"key":"656_CR3","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1038\/nature08490","volume":"461","author":"LA Weiss","year":"2009","unstructured":"Weiss LA, Arking DE, Gene Discovery Project of Johns H, the Autism C, Daly MJ, Chakravarti A. A genome-wide linkage and association scan reveals novel loci for autism. Nature 2009;461:802\u20138.","journal-title":"Nature"},{"key":"656_CR4","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1038\/nature09146","volume":"466","author":"D Pinto","year":"2010","unstructured":"Pinto D, Pagnamenta AT, Klei L, Anney R, Merico D, Regan R, et al. Functional impact of global rare copy number variation in autism spectrum disorders. Nature 2010;466:368\u201372.","journal-title":"Nature"},{"key":"656_CR5","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1038\/nn.4524","volume":"20","author":"RKC Yuen","year":"2017","unstructured":"Yuen RKC, Merico D, Bookman MJLH, Thiruvahindrapuram B, Patel RV, et al. Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder. Nat Neurosci. 2017;20:602\u201311.","journal-title":"Nat Neurosci"},{"key":"656_CR6","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1038\/ng.2711","volume":"45","author":"SH Lee","year":"2013","unstructured":"Cross-Disorder Group of the Psychiatric Genomics C, Lee SH, Ripke S, Neale BM, Faraone SV, Purcell SM, et al. Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nat Genet 2013;45:984.","journal-title":"Nat Genet"},{"key":"656_CR7","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1126\/science.aad6469","volume":"359","author":"MJ Gandal","year":"2018","unstructured":"Gandal MJ, Haney JR, Parikshak NN, Leppa V, Ramaswami G, Hartl C, et al. Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap. Science 2018;359:693\u201397.","journal-title":"Science"},{"key":"656_CR8","first-page":"23","volume":"78","author":"Fmr1 knockout mice: a model to study fragile X mental retardation.","year":"1994","unstructured":"Fmr1 knockout mice: a model to study fragile X mental retardation. The Dutch-Belgian Fragile X Consortium. Cell 1994;78:23\u201333.","journal-title":"Cell"},{"key":"656_CR9","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1038\/85899","volume":"27","author":"J Guy","year":"2001","unstructured":"Guy J, Hendrich B, Holmes M, Martin JE, Bird A. A mouse Mecp2-null mutation causes neurological symptoms that mimic Rett syndrome. Nat Genet 2001;27:322.","journal-title":"Nat Genet"},{"key":"656_CR10","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1038\/nature09965","volume":"472","author":"J Pe\u00e7a","year":"2011","unstructured":"Pe\u00e7a J, Feliciano C, Ting JT, Wang W, Wells MF, Venkatraman TN, et al. Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature 2011;472:437.","journal-title":"Nature"},{"key":"656_CR11","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1093\/hmg\/11.5.525","volume":"11","author":"DJ Kwiatkowski","year":"2002","unstructured":"Kwiatkowski DJ, Zhang H, Bandura JL, Heiberger KM, Glogauer M, el-Hashemite N, et al. A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells. Hum Mol Genet. 2002;11:525\u201334.","journal-title":"Hum Mol Genet"},{"key":"656_CR12","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1172\/JCI7319","volume":"104","author":"H Onda","year":"1999","unstructured":"Onda H, Lueck A, Marks PW, Warren HB, Kwiatkowski DJ. Tsc2(+\/\u2212) mice develop tumors in multiple sites that express gelsolin and are influenced by genetic background. J Clin Invest. 1999;104:687\u201395.","journal-title":"J Clin Invest"},{"key":"656_CR13","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1111\/j.1601-183X.2007.00330.x","volume":"7","author":"HG McFarlane","year":"2008","unstructured":"McFarlane HG, Kusek GK, Yang M, Phoenix JL, Bolivar VJ, Crawley JN. Autism-like behavioral phenotypes in BTBR T+tf\/J mice. Genes Brain Behav. 2008;7:152\u201363.","journal-title":"Genes Brain Behav"},{"key":"656_CR14","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1038\/nrn2851","volume":"11","author":"JL Silverman","year":"2010","unstructured":"Silverman JL, Yang M, Lord C, Crawley JN. Behavioural phenotyping assays for mouse models of autism. Nat Rev Neurosci. 2010;11:490\u2013502.","journal-title":"Nat Rev Neurosci"},{"key":"656_CR15","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.bbr.2018.03.014","volume":"347","author":"OY Chao","year":"2018","unstructured":"Chao OY, Yunger R, Yang YM. Behavioral assessments of BTBR T+Itpr3tf\/J mice by tests of object attention and elevated open platform: implications for an animal model of psychiatric comorbidity in autism. Behav Brain Res. 2018;347:140\u201347.","journal-title":"Behav Brain Res"},{"key":"656_CR16","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/j.neuroimage.2012.12.029","volume":"70","author":"J Ellegood","year":"2013","unstructured":"Ellegood J, Babineau BA, Henkelman RM, Lerch JP, Crawley JN. Neuroanatomical analysis of the BTBR mouse model of autism using magnetic resonance imaging and diffusion tensor imaging. Neuroimage 2013;70:288\u2013300.","journal-title":"Neuroimage"},{"key":"656_CR17","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.neubiorev.2016.12.037","volume":"76","author":"KZ Meyza","year":"2017","unstructured":"Meyza KZ, Blanchard DC. The BTBR mouse model of idiopathic autism\u2014current view on mechanisms. Neurosci Biobehav Rev. 2017;76:99\u2013110.","journal-title":"Neurosci Biobehav Rev"},{"key":"656_CR18","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1007\/s12311-012-0355-9","volume":"11","author":"SH Fatemi","year":"2012","unstructured":"Fatemi SH, Aldinger KA, Ashwood P, Bauman ML, Blaha CD, Blatt GJ, et al. Consensus paper: pathological role of the cerebellum in autism. Cerebellum 2012;11:777\u2013807.","journal-title":"Cerebellum"},{"key":"656_CR19","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.neuron.2014.07.016","volume":"83","author":"SS Wang","year":"2014","unstructured":"Wang SS, Kloth AD, Badura A. The cerebellum, sensitive periods, and autism. Neuron 2014;83:518\u201332.","journal-title":"Neuron"},{"key":"656_CR20","doi-asserted-by":"crossref","first-page":"420","DOI":"10.3389\/fnins.2015.00420","volume":"9","author":"DR Hampson","year":"2015","unstructured":"Hampson DR, Blatt GJ. Autism spectrum disorders and neuropathology of the cerebellum. Front Neurosci 2015;9:420.","journal-title":"Front Neurosci"},{"key":"656_CR21","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.ijdevneu.2004.09.006","volume":"23","author":"ML Bauman","year":"2005","unstructured":"Bauman ML, Kemper TL. Neuroanatomic observations of the brain in autism: a review and future directions. Int J Dev Neurosci. 2005;23:183\u20137.","journal-title":"Int J Dev Neurosci"},{"key":"656_CR22","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.pscychresns.2008.06.001","volume":"172","author":"SJ Webb","year":"2009","unstructured":"Webb SJ, Sparks BF, Friedman SD, Shaw DW, Giedd J, Dawson G, et al. Cerebellar vermal volumes and behavioral correlates in children with autism spectrum disorder. Psychiatry Res 2009;172:61\u20137.","journal-title":"Psychiatry Res"},{"key":"656_CR23","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1097\/00004583-200106000-00011","volume":"40","author":"AY Hardan","year":"2001","unstructured":"Hardan AY, Minshew NJ, Harenski K, Keshavan MS. Posterior fossa magnetic resonance imaging in autism. J Am Acad Child Adolesc Psychiatry. 2001;40:666\u201372.","journal-title":"J Am Acad Child Adolesc Psychiatry"},{"key":"656_CR24","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1093\/brain\/123.11.2203","volume":"123","author":"HD Critchley","year":"2000","unstructured":"Critchley HD, Daly EM, Bullmore ET, Williams SC, Van Amelsvoort T, Robertson DM, et al. The functional neuroanatomy of social behaviour: changes in cerebral blood flow when people with autistic disorder process facial expressions. Brain 2000;123:2203\u201312.","journal-title":"Brain"},{"key":"656_CR25","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1176\/appi.ajp.160.2.262","volume":"160","author":"G Allen","year":"2003","unstructured":"Allen G, Courchesne E. Differential effects of developmental cerebellar abnormality on cognitive and motor functions in the cerebellum: an fMRI study of autism. Am J Psychiatry. 2003;160:262\u201373.","journal-title":"Am J Psychiatry"},{"key":"656_CR26","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.biopsych.2015.03.024","volume":"78","author":"AJ Khan","year":"2015","unstructured":"Khan AJ, Nair A, Keown CL, Datko MC, Lincoln AJ, Muller RA. Cerebro-cerebellar resting-state functional connectivity in children and adolescents with autism spectrum disorder. Biol Psychiatry 2015;78:625\u201334.","journal-title":"Biol Psychiatry"},{"key":"656_CR27","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/nature11310","volume":"488","author":"PT Tsai","year":"2012","unstructured":"Tsai PT, Hull C, Chu Y, Greene-Colozzi E, Sadowski AR, Leech JM, et al. Autistic-like behaviour and cerebellar dysfunction in Purkinje cell Tsc1 mutant mice. Nature 2012;488:647\u201351.","journal-title":"Nature"},{"key":"656_CR28","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1038\/npp.2015.339","volume":"41","author":"D Cupolillo","year":"2016","unstructured":"Cupolillo D, Hoxha E, Faralli A, De Luca A, Rossi F, Tempia F, et al. Autistic-like traits and cerebellar dysfunction in Purkinje cell PTEN knock-out mice. Neuropsychopharmacology 2016;41:1457\u201366.","journal-title":"Neuropsychopharmacology"},{"key":"656_CR29","volume":"7","author":"S Peter","year":"2016","unstructured":"Peter S, Ten Brinke MM, Stedehouder J, Reinelt CM, Wu B, Zhou H, et al. Dysfunctional cerebellar Purkinje cells contribute to autism-like behaviour in Shank2-deficient mice. Nat Commun 2016;7:12627.","journal-title":"Nat Commun"},{"key":"656_CR30","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1038\/s41593-017-0004-1","volume":"20","author":"CJ Stoodley","year":"2017","unstructured":"Stoodley CJ, D\u2019Mello AM, Ellegood J, Jakkamsetti V, Liu P, Nebel MB, et al. Altered cerebellar connectivity in autism and cerebellar-mediated rescue of autism-related behaviors in mice. Nat Neurosci 2017;20:1744\u201351.","journal-title":"Nat Neurosci"},{"key":"656_CR31","doi-asserted-by":"crossref","unstructured":"Yang Y-M, Arsenault J, Bah A, Krzeminski M, Fekete A, Chao OY, et al. Identification of a molecular locus for normalizing dysregulated GABA release from interneurons in the Fragile X brain. Mol Psychiatry 2018;1\u201319.","DOI":"10.1038\/s41380-018-0240-0"},{"key":"656_CR32","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.omtm.2017.07.006","volume":"6","author":"K Nitta","year":"2017","unstructured":"Nitta K, Matsuzaki Y, Konno A, Hirai H. Minimal Purkinje cell-specific PCP2\/L7 promoter virally available for rodents and non-human primates. Mol Ther Methods Clin Dev. 2017;6:159\u201370.","journal-title":"Mol Ther Methods Clin Dev"},{"key":"656_CR33","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.neuron.2016.01.040","volume":"89","author":"BL Roth","year":"2016","unstructured":"Roth BL. DREADDs for neuroscientists. Neuron 2016;89:683\u201394.","journal-title":"Neuron"},{"key":"656_CR34","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0014-2999(03)01272-X","volume":"463","author":"L Prut","year":"2003","unstructured":"Prut L, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur J Pharm. 2003;463:3\u201333.","journal-title":"Eur J Pharm"},{"key":"656_CR35","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/s41583-019-0152-2","volume":"20","author":"A Sathyanesan","year":"2019","unstructured":"Sathyanesan A, Zhou J, Scafidi J, Heck DH, Sillitoe RV, Gallo V. Emerging connections between cerebellar development, behaviour and complex brain disorders. Nat Rev Neurosci. 2019;20:298\u2013313.","journal-title":"Nat Rev Neurosci"},{"key":"656_CR36","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1146\/annurev-neuro-070918-050258","volume":"42","author":"JD Schmahmann","year":"2019","unstructured":"Schmahmann JD, Guell X, Stoodley CJ, Halko MA. The theory and neuroscience of cerebellar cognition. Annu Rev Neurosci. 2019;42:337\u201364.","journal-title":"Annu Rev Neurosci"},{"key":"656_CR37","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/S0896-6273(00)80379-7","volume":"19","author":"M Hausser","year":"1997","unstructured":"Hausser M, Clark BA. Tonic synaptic inhibition modulates neuronal output pattern and spatiotemporal synaptic integration. Neuron 1997;19:665\u201378.","journal-title":"Neuron"},{"key":"656_CR38","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1162\/089976603322385063","volume":"15","author":"J Benda","year":"2003","unstructured":"Benda J, Herz AV. A universal model for spike-frequency adaptation. Neural Comput 2003;15:2523\u201364.","journal-title":"Neural Comput"},{"key":"656_CR39","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/nrn2148","volume":"8","author":"BP Bean","year":"2007","unstructured":"Bean BP. The action potential in mammalian central neurons. Nat Rev Neurosci. 2007;8:451\u201365.","journal-title":"Nat Rev Neurosci"},{"key":"656_CR40","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1152\/jn.01098.2005","volume":"97","author":"F Santamaria","year":"2007","unstructured":"Santamaria F, Tripp PG, Bower JM. Feedforward inhibition controls the spread of granule cell-induced Purkinje cell activity in the cerebellar cortex. J Neurophysiol 2007;97:248\u201363.","journal-title":"J Neurophysiol"},{"key":"656_CR41","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.tins.2010.08.004","volume":"33","author":"H Jorntell","year":"2010","unstructured":"Jorntell H, Bengtsson F, Schonewille M, De Zeeuw CI. Cerebellar molecular layer interneurons\u2014computational properties and roles in learning. Trends Neurosci 2010;33:524\u201332.","journal-title":"Trends Neurosci"},{"key":"656_CR42","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1038\/nrn1938","volume":"7","author":"HC Lai","year":"2006","unstructured":"Lai HC, Jan LY. The distribution and targeting of neuronal voltage-gated ion channels. Nat Rev Neurosci. 2006;7:548\u201362.","journal-title":"Nat Rev Neurosci"},{"key":"656_CR43","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/365075a0","volume":"365","author":"H Wang","year":"1993","unstructured":"Wang H, Kunkel DD, Martin TM, Schwartzkroin PA, Tempel BL. Heteromultimeric K+ channels in terminal and juxtaparanodal regions of neurons. Nature 1993;365:75\u20139.","journal-title":"Nature"},{"key":"656_CR44","doi-asserted-by":"crossref","first-page":"2408","DOI":"10.1523\/JNEUROSCI.14-04-02408.1994","volume":"14","author":"M Sheng","year":"1994","unstructured":"Sheng M, Tsaur ML, Jan YN, Jan LY. Contrasting subcellular localization of the Kv1.2 K+ channel subunit in different neurons of rat brain. J Neurosci 1994;14:2408\u201317.","journal-title":"J Neurosci"},{"key":"656_CR45","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1038\/sj.bjp.0702218","volume":"125","author":"AP Southan","year":"1998","unstructured":"Southan AP, Robertson B. Modulation of inhibitory post-synaptic currents (IPSCs) in mouse cerebellar Purkinje and basket cells by snake and scorpion toxin K+ channel blockers. Br J Pharm. 1998;125:1375\u201381.","journal-title":"Br J Pharm"},{"key":"656_CR46","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1523\/JNEUROSCI.20-01-00114.2000","volume":"20","author":"AP Southan","year":"2000","unstructured":"Southan AP, Robertson B. Electrophysiological characterization of voltage-gated K(+) currents in cerebellar basket and purkinje cells: Kv1 and Kv3 channel subfamilies are present in basket cell nerve terminals. J Neurosci 2000;20:114\u201322.","journal-title":"J Neurosci"},{"key":"656_CR47","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0006-8993(01)02068-6","volume":"895","author":"YH Chung","year":"2001","unstructured":"Chung YH, Shin C, Kim MJ, Lee BK, Cha CI. Immunohistochemical study on the distribution of six members of the Kv1 channel subunits in the rat cerebellum. Brain Res 2001;895:173\u20137.","journal-title":"Brain Res"},{"key":"656_CR48","doi-asserted-by":"crossref","first-page":"20055","DOI":"10.1073\/pnas.0708574104","volume":"104","author":"JW Yang","year":"2007","unstructured":"Yang JW, Vacher H, Park KS, Clark E, Trimmer JS. Trafficking-dependent phosphorylation of Kv1.2 regulates voltage-gated potassium channel cell surface expression. Proc Natl Acad Sci USA. 2007;104:20055\u201360.","journal-title":"Proc Natl Acad Sci USA"},{"key":"656_CR49","doi-asserted-by":"crossref","first-page":"32160","DOI":"10.1074\/jbc.M110.153676","volume":"285","author":"G Xie","year":"2010","unstructured":"Xie G, Harrison J, Clapcote SJ, Huang Y, Zhang JY, Wang LY, et al. A new Kv1.2 channelopathy underlying cerebellar ataxia. J Biol Chem. 2010;285:32160\u201373.","journal-title":"J Biol Chem"},{"key":"656_CR50","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1038\/nature05416","volume":"444","author":"D Schmidt","year":"2006","unstructured":"Schmidt D, Jiang QX, MacKinnon R. Phospholipids and the origin of cationic gating charges in voltage sensors. Nature 2006;444:775\u20139.","journal-title":"Nature"},{"key":"656_CR51","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.1529\/biophysj.108.130757","volume":"95","author":"SI Borjesson","year":"2008","unstructured":"Borjesson SI, Hammarstrom S, Elinder F. Lipoelectric modification of ion channel voltage gating by polyunsaturated fatty acids. Biophys J 2008;95:2242\u201353.","journal-title":"Biophys J"},{"key":"656_CR52","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/nature13241","volume":"509","author":"LN Nguyen","year":"2014","unstructured":"Nguyen LN, Ma D, Shui G, Wong P, Cazenave-Gassiot A, Zhang X, et al. Mfsd2a is a transporter for the essential omega-3 fatty acid docosahexaenoic acid. Nature 2014;509:503\u20136.","journal-title":"Nature"},{"key":"656_CR53","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.tips.2008.07.005","volume":"29","author":"A Ramos","year":"2008","unstructured":"Ramos A. Animal models of anxiety: do I need multiple tests? Trends Pharm Sci. 2008;29:493\u20138.","journal-title":"Trends Pharm Sci"},{"key":"656_CR54","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1056\/NEJM198805263182102","volume":"318","author":"E Courchesne","year":"1988","unstructured":"Courchesne E, Yeung-Courchesne R, Press GA, Hesselink JR, Jernigan TL. Hypoplasia of cerebellar vermal lobules VI and VII in autism. N Engl J Med. 1988;318:1349\u201354.","journal-title":"N Engl J Med"},{"key":"656_CR55","doi-asserted-by":"crossref","first-page":"e36401","DOI":"10.7554\/eLife.36401","volume":"7","author":"A Badura","year":"2018","unstructured":"Badura A, Verpeut JL, Metzger JW, Pereira TD, Pisano TJ, Deverett B, et al. Normal cognitive and social development require posterior cerebellar activity. Elife. 2018;7:e36401.","journal-title":"Elife"},{"key":"656_CR56","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1016\/j.neuron.2014.01.016","volume":"81","author":"S Han","year":"2014","unstructured":"Han S, Tai C, Jones CJ, Scheuer T, Catterall WA. Enhancement of inhibitory neurotransmission by GABAA receptors having alpha2,3-subunits ameliorates behavioral deficits in a mouse model of autism. Neuron 2014;81:1282\u201389.","journal-title":"Neuron"},{"key":"656_CR57","doi-asserted-by":"crossref","first-page":"324","DOI":"10.3389\/fphys.2015.00324","volume":"6","author":"CM Daimon","year":"2015","unstructured":"Daimon CM, Jasien JM, Wood WH 3rd, Zhang Y, Becker KG, Silverman JL, et al. Hippocampal transcriptomic and proteomic alterations in the BTBR mouse model of autism spectrum disorder. Front Physiol 2015;6:324.","journal-title":"Front Physiol"},{"key":"656_CR58","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1212\/WNL.0b013e3182166dc7","volume":"76","author":"DK Sokol","year":"2011","unstructured":"Sokol DK, Maloney B, Long JM, Ray B, Lahiri DK. Autism, Alzheimer disease, and fragile X: APP, FMRP, and mGluR5 are molecular links. Neurology 2011;76:1344\u201352.","journal-title":"Neurology"},{"key":"656_CR59","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/nrneurol.2016.81","volume":"12","author":"PB Crino","year":"2016","unstructured":"Crino PB. The mTOR signalling cascade: paving new roads to cure neurological disease. Nat Rev Neurol. 2016;12:379\u201392.","journal-title":"Nat Rev Neurol"},{"key":"656_CR60","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/S0896-6273(00)80969-1","volume":"19","author":"IM Raman","year":"1997","unstructured":"Raman IM, Sprunger LK, Meisler MH, Bean BP. Altered subthreshold sodium currents and disrupted firing patterns in Purkinje neurons of Scn8a mutant mice. Neuron 1997;19:881\u201391.","journal-title":"Neuron"},{"key":"656_CR61","doi-asserted-by":"crossref","first-page":"4899","DOI":"10.1523\/JNEUROSCI.23-12-04899.2003","volume":"23","author":"ZM Khaliq","year":"2003","unstructured":"Khaliq ZM, Gouwens NW, Raman IM. The contribution of resurgent sodium current to high-frequency firing in Purkinje neurons: an experimental and modeling study. J Neurosci 2003;23:4899\u2013912.","journal-title":"J Neurosci"},{"key":"656_CR62","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1113\/jphysiol.2002.027854","volume":"548","author":"JR Edgerton","year":"2003","unstructured":"Edgerton JR, Reinhart PH. Distinct contributions of small and large conductance Ca2+-activated K+ channels to rat Purkinje neuron function. J Physiol 2003;548:53\u201369.","journal-title":"J Physiol"},{"key":"656_CR63","doi-asserted-by":"crossref","first-page":"1080","DOI":"10.1124\/mol.54.6.1080","volume":"54","author":"SI McDonough","year":"1998","unstructured":"McDonough SI, Bean BP. Mibefradil inhibition of T-type calcium channels in cerebellar purkinje neurons. Mol Pharmacol 1998;54:1080\u20137.","journal-title":"Mol Pharmacol"},{"key":"656_CR64","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/S0092-8674(03)00884-5","volume":"115","author":"MF Nolan","year":"2003","unstructured":"Nolan MF, Malleret G, Lee KH, Gibbs E, Dudman JT, Santoro B, et al. The hyperpolarization-activated HCN1 channel is important for motor learning and neuronal integration by cerebellar Purkinje cells. Cell 2003;115:551\u201364.","journal-title":"Cell"},{"key":"656_CR65","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/sj.mp.4001241","volume":"8","author":"LA Weiss","year":"2003","unstructured":"Weiss LA, Escayg A, Kearney JA, Trudeau M, MacDonald BT, Mori M, et al. Sodium channels SCN1A, SCN2A and SCN3A in familial autism. Mol Psychiatry 2003;8:186\u201394.","journal-title":"Mol Psychiatry"},{"key":"656_CR66","doi-asserted-by":"crossref","first-page":"22085","DOI":"10.1074\/jbc.M603316200","volume":"281","author":"I Splawski","year":"2006","unstructured":"Splawski I, Yoo DS, Stotz SC, Cherry A, Clapham DE, Keating MT. CACNA1H mutations in autism spectrum disorders. J Biol Chem. 2006;281:22085\u201391.","journal-title":"J Biol Chem"},{"key":"656_CR67","doi-asserted-by":"crossref","first-page":"174","DOI":"10.3389\/fncel.2015.00071","volume":"6","author":"JC DiFrancesco","year":"2015","unstructured":"DiFrancesco JC, DiFrancesco D. Dysfunctional HCN ion channels in neurological diseases. Front Cell Neurosci. 2015;6:174.","journal-title":"Front Cell Neurosci"},{"key":"656_CR68","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.celrep.2018.09.039","volume":"25","author":"PT Tsai","year":"2018","unstructured":"Tsai PT, Rudolph S, Guo C, Ellegood J, Gibson JM, Schaeffer SM, et al. Sensitive periods for cerebellar-mediated autistic-like behaviors. Cell Rep. 2018;25:357\u201367.","journal-title":"Cell Rep."},{"key":"656_CR69","doi-asserted-by":"crossref","first-page":"e37102","DOI":"10.7554\/eLife.37102","volume":"8","author":"HL Payne","year":"2019","unstructured":"Payne HL, French RL, Guo CC, Nguyen-Vu TB, Manninen T, Raymond JL. Cerebellar Purkinje cells control eye movements with a rapid rate code that is invariant to spike irregularity. Elife. 2019;8:e37102.","journal-title":"Elife"},{"key":"656_CR70","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0006-8993(03)02354-0","volume":"971","author":"D Wahlsten","year":"2003","unstructured":"Wahlsten D, Metten P, Crabbe JC. Survey of 21 inbred mouse strains in two laboratories reveals that BTBR T\/+ tf\/tf has severely reduced hippocampal commissure and absent corpus callosum. Brain Res 2003;971:47\u201354.","journal-title":"Brain Res"},{"key":"656_CR71","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1007\/s10803-012-1653-2","volume":"43","author":"YC Lau","year":"2013","unstructured":"Lau YC, Hinkley LB, Bukshpun P, Strominger ZA, Wakahiro ML, Baron-Cohen S, et al. Autism traits in individuals with agenesis of the corpus callosum. J Autism Dev Disord. 2013;43:1106\u201318.","journal-title":"J Autism Dev Disord"},{"key":"656_CR72","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1093\/brain\/awu070","volume":"137","author":"LK Paul","year":"2014","unstructured":"Paul LK, Corsello C, Kennedy DP, Adolphs R. Agenesis of the corpus callosum and autism: a comprehensive comparison. Brain 2014;137:1813\u201329.","journal-title":"Brain"},{"key":"656_CR73","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1111\/j.1460-9568.2009.06714.x","volume":"29","author":"M Yang","year":"2009","unstructured":"Yang M, Clarke AM, Crawley JN. Postnatal lesion evidence against a primary role for the corpus callosum in mouse sociability. Eur J Neurosci. 2009;29:1663\u201377.","journal-title":"Eur J Neurosci"},{"key":"656_CR74","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.brainres.2013.04.001","volume":"1513","author":"VM Miller","year":"2013","unstructured":"Miller VM, Gupta D, Neu N, Cotroneo A, Boulay CB, Seegal RF. Novel inter-hemispheric white matter connectivity in the BTBR mouse model of autism. Brain Res 2013;1513:26\u201333.","journal-title":"Brain Res"},{"key":"656_CR75","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/j.neuron.2005.07.005","volume":"47","author":"SK Koekkoek","year":"2005","unstructured":"Koekkoek SK, Yamaguchi K, Milojkovic BA, Dortland BR, Ruigrok TJ, Maex R, et al. Deletion of FMR1 in Purkinje cells enhances parallel fiber LTD, enlarges spines, and attenuates cerebellar eyelid conditioning in Fragile X syndrome. Neuron 2005;47:339\u201352.","journal-title":"Neuron"},{"key":"656_CR76","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.braindev.2007.03.002","volume":"29","author":"X Ming","year":"2007","unstructured":"Ming X, Brimacombe M, Wagner GC. Prevalence of motor impairment in autism spectrum disorders. Brain Dev 2007;29:565\u201370.","journal-title":"Brain Dev"},{"key":"656_CR77","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms6586","volume":"5","author":"C Piochon","year":"2014","unstructured":"Piochon C, Kloth AD, Grasselli G, Titley HK, Nakayama H, Hashimoto K, et al. Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism. Nat Commun 2014;5:5586.","journal-title":"Nat Commun"},{"key":"656_CR78","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1007\/s11427-015-4894-4","volume":"58","author":"MW Mosconi","year":"2015","unstructured":"Mosconi MW, Sweeney JA. Sensorimotor dysfunctions as primary features of autism spectrum disorders. Sci China Life Sci. 2015;58:1016\u201323.","journal-title":"Sci China Life Sci"},{"key":"656_CR79","doi-asserted-by":"crossref","first-page":"9228","DOI":"10.1523\/JNEUROSCI.6504-11.2012","volume":"32","author":"MR Williams","year":"2012","unstructured":"Williams MR, Fuchs JR, Green JT, Morielli AD. Cellular mechanisms and behavioral consequences of Kv1.2 regulation in the rat cerebellum. J Neurosci 2012;32:9228\u201337.","journal-title":"J Neurosci"},{"key":"656_CR80","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.nlm.2017.05.009","volume":"142","author":"JR Fuchs","year":"2017","unstructured":"Fuchs JR, Darlington SW, Green JT, Morielli AD. Cerebellar learning modulates surface expression of a voltage-gated ion channel in cerebellar cortex. Neurobiol Learn Mem. 2017;142:252\u201362.","journal-title":"Neurobiol Learn Mem"},{"key":"656_CR81","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1007\/BF02172283","volume":"24","author":"LL Sears","year":"1994","unstructured":"Sears LL, Finn PR, Steinmetz JE. Abnormal classical eye-blink conditioning in autism. J Autism Dev Disord. 1994;24:737\u201351.","journal-title":"J Autism Dev Disord"},{"key":"656_CR82","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.biopsych.2006.05.007","volume":"61","author":"GP Amminger","year":"2007","unstructured":"Amminger GP, Berger GE, Schafer MR, Klier C, Friedrich MH, Feucht M. Omega-3 fatty acids supplementation in children with autism: a double-blind randomized, placebo-controlled pilot study. Biol Psychiatry 2007;61:551\u20133.","journal-title":"Biol Psychiatry"},{"key":"656_CR83","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1007\/s10803-009-0724-5","volume":"39","author":"S Bent","year":"2009","unstructured":"Bent S, Bertoglio K, Hendren RL. Omega-3 fatty acids for autistic spectrum disorder: a systematic review. J Autism Dev Disord. 2009;39:1145\u201354.","journal-title":"J Autism Dev Disord"},{"key":"656_CR84","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/s41583-018-0002-7","volume":"19","author":"AC Bostan","year":"2018","unstructured":"Bostan AC, Strick PL. The basal ganglia and the cerebellum: nodes in an integrated network. Nat Rev Neurosci. 2018;19:338\u201350.","journal-title":"Nat Rev Neurosci"}],"container-title":["Neuropsychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41386-020-0656-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41386-020-0656-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41386-020-0656-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T21:08:41Z","timestamp":1684616921000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41386-020-0656-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,16]]},"references-count":84,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["656"],"URL":"https:\/\/doi.org\/10.1038\/s41386-020-0656-5","relation":{},"ISSN":["0893-133X","1740-634X"],"issn-type":[{"value":"0893-133X","type":"print"},{"value":"1740-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,16]]},"assertion":[{"value":"10 December 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 February 2020","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 March 2020","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2020","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}