{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T21:03:02Z","timestamp":1782421382927,"version":"3.54.5"},"reference-count":83,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"crossref","award":["2021A1515012498"],"award-info":[{"award-number":["2021A1515012498"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"crossref","award":["2016A030308020"],"award-info":[{"award-number":["2016A030308020"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Medical Research Fund of Guangdong Province","award":["A2020126"],"award-info":[{"award-number":["A2020126"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82071503"],"award-info":[{"award-number":["82071503"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Key Scientific and Technological Projects of Guangdong Province","award":["2018B030335001"],"award-info":[{"award-number":["2018B030335001"]}]},{"name":"Guangdong Basic and Applied Research Foundation","award":["2019B1515120080"],"award-info":[{"award-number":["2019B1515120080"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Biol"],"DOI":"10.1186\/s12915-025-02224-9","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T08:16:18Z","timestamp":1751357778000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["doc2a and doc2b contribute to locomotor and social behaviors by down-regulating npas4b in zebrafish"],"prefix":"10.1186","volume":"23","author":[{"given":"Yali","family":"Chi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixin","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haihua","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanshan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinping","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4086-4180","authenticated-orcid":false,"given":"Liping","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"2224_CR1","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1001\/archgenpsychiatry.2009.80","volume":"66","author":"A Guilmatre","year":"2009","unstructured":"Guilmatre A, Dubourg C, Mosca AL, Legallic S, Goldenberg A, Drouin-Garraud V, et al. Recurrent rearrangements in synaptic and neurodevelopmental genes and shared biologic pathways in schizophrenia, autism, and mental retardation. Arch Gen Psychiatry. 2009;66:947\u201356.","journal-title":"Arch Gen Psychiatry"},{"key":"2224_CR2","doi-asserted-by":"crossref","unstructured":"Niarchou M, Chawner S, Doherty JL, Maillard AM, Jacquemont S, Chung WK, et al. Psychiatric disorders in children with 16p11.2 deletion and duplication. Transl Psychiatry. 2019;9:8.","DOI":"10.1038\/s41398-018-0339-8"},{"key":"2224_CR3","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1126\/science.1138659","volume":"316","author":"J Sebat","year":"2007","unstructured":"Sebat J, Lakshmi B, Malhotra D, Troge J, Lese-Martin C, Walsh T, et al. Strong association of de novo copy number mutations with autism. Science. 2007;316:445\u20139.","journal-title":"Science"},{"key":"2224_CR4","doi-asserted-by":"crossref","unstructured":"Kumar RA, KaraMohamed S, Sudi J, Conrad DF, Brune C, Badner JA, et al. Recurrent 16p11.2 microdeletions in autism. Hum Mol Genet. 2008;17:628\u2013638.","DOI":"10.1093\/hmg\/ddm376"},{"key":"2224_CR5","doi-asserted-by":"crossref","unstructured":"Weiss LA, Shen Y, Korn JM, Arking, DE, Miller, DT, Fossdal R, et al. Association between microdeletion and microduplication at 16p11.2 and autism. N Engl J Med. 2008;358: 667\u2013675.","DOI":"10.1056\/NEJMoa075974"},{"key":"2224_CR6","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1038\/nature07953","volume":"459","author":"JT Glessner","year":"2009","unstructured":"Glessner JT, Wang K, Cai G, Korvatska O, Kim CE, Wood S, et al. Autism genome-wide copy number variation reveals ubiquitin and neuronal genes. Nature. 2009;459:569\u201373.","journal-title":"Nature"},{"key":"2224_CR7","doi-asserted-by":"crossref","unstructured":"Walsh KM, Bracken MB. Copy number variation in the dosage-sensitive 16p11.2 interval accounts for only a small proportion of autism incidence: a systematic review and meta-analysis. Genet Med. 2011;13:377\u2013384.","DOI":"10.1097\/GIM.0b013e3182076c0c"},{"key":"2224_CR8","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1038\/mp.2011.154","volume":"17","author":"G Kirov","year":"2012","unstructured":"Kirov G, Pocklington AJ, Holmans P, Ivanov D, Ikeda M, Ruderfer D, et al. De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia. Mol Psychiatry. 2012;17:142\u201353.","journal-title":"Mol Psychiatry"},{"key":"2224_CR9","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1192\/bjp.bp.113.131052","volume":"204","author":"E Rees","year":"2014","unstructured":"Rees E, Walters JT, Georgieva L, Isles AR, Chambert KD, Richards AL, et al. Analysis of copy number variations at 15 schizophrenia-associated loci. Br J Psychiatry. 2014;204:108\u201314.","journal-title":"Br J Psychiatry"},{"key":"2224_CR10","doi-asserted-by":"crossref","unstructured":"Crespi B, Badcock C. 2008 Psychosis and autism as diametrical disorders of the social brain. Behav. Brain Sci. 31(3), 241\u2013261; discussion 261\u2013320.","DOI":"10.1017\/S0140525X08004214"},{"issue":"241\u2013261","key":"2224_CR11","first-page":"261","volume":"31","author":"B Crespi","year":"2008","unstructured":"Crespi B, Badcock C. Psychosis and autism as diametrical disorders of the social brain. Behav Brain Sci. 2008;31(241\u2013261):261\u2013320.","journal-title":"Behav Brain Sci"},{"key":"2224_CR12","doi-asserted-by":"crossref","unstructured":"Shinawi M, Liu P, Kang SH, Shen J, Belmont JW, Scott DA, et al. Recurrent reciprocal 16p11.2 rearrangements associated with global developmental delay, behavioural problems, dysmorphism, epilepsy, and abnormal head size. J Med Genet. 2010;47:332\u2013341.","DOI":"10.1136\/jmg.2009.073015"},{"key":"2224_CR13","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1016\/j.cell.2012.02.039","volume":"148","author":"D Malhotra","year":"2012","unstructured":"Malhotra D, Sebat J. CNVs: harbingers of a rare variant revolution in psychiatric genetics. Cell. 2012;148:1223\u201341.","journal-title":"Cell"},{"key":"2224_CR14","doi-asserted-by":"crossref","unstructured":"Hudac CM, Bove J, Barber S, Duyzend M, Wallace A, Martin CL, et al. Evaluating heterogeneity in ASD symptomatology, cognitive ability, and adaptive functioning among 16p11.2 CNV carriers. Autism Res. 2020;13:1300\u20131310.","DOI":"10.1002\/aur.2332"},{"key":"2224_CR15","doi-asserted-by":"crossref","unstructured":"Blaker -Lee A, Gupta S, McCammon JM, De Rienzo G, Sive H. Zebrafish homologs of genes within 16p11.2, a genomic region associated with brain disorders, are active during brain development, and include two deletion dosage sensor genes. Dis Model Mech. 2012;5:834\u2013851.","DOI":"10.1242\/dmm.009944"},{"key":"2224_CR16","doi-asserted-by":"crossref","unstructured":"Blumenthal I, Ragavendran A, Erdin S, Klei L, Sugathan A, Guide JR, et al. Transcriptional Consequences of 16p11.2 Deletion and Duplication in Mouse Cortex and Multiplex Autism Families. The American Journal of Human Genetics. 2014;94:870\u2013883.","DOI":"10.1016\/j.ajhg.2014.05.004"},{"key":"2224_CR17","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.neuron.2011.03.011","volume":"70","author":"ZP Pang","year":"2011","unstructured":"Pang ZP, Bacaj T, Yang X, Zhou P, Xu W, Sudhof TC. Doc2 supports spontaneous synaptic transmission by a Ca(2+)-independent mechanism. Neuron. 2011;70:244\u201351.","journal-title":"Neuron"},{"key":"2224_CR18","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1038\/nature24470","volume":"551","author":"CO Escamilla","year":"2017","unstructured":"Escamilla CO, Filonova I, Walker AK, Xuan ZX, Holehonnur R, Espinosa F, et al. Kctd13 deletion reduces synaptic transmission via increased RhoA. Nature. 2017;551:227\u201331.","journal-title":"Nature"},{"key":"2224_CR19","doi-asserted-by":"crossref","unstructured":"Falcicchia C, Tozzi F, Arancio O, Watterson DM, Origlia N. Involvement of p38 MAPK in Synaptic Function and Dysfunction. Int J Mol Sci. 2020;21.","DOI":"10.3390\/ijms21165624"},{"key":"2224_CR20","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1016\/j.cell.2011.09.046","volume":"147","author":"J Yao","year":"2011","unstructured":"Yao J, Gaffaney JD, Kwon SE, Chapman ER. Doc2 is a Ca2+ sensor required for asynchronous neurotransmitter release. Cell. 2011;147:666\u201377.","journal-title":"Cell"},{"key":"2224_CR21","doi-asserted-by":"crossref","unstructured":"van Westen R, Poppinga J, Diez AR, Toonen RF, Verhage M. Neuromodulator release in neurons requires two functionally redundant calcium sensors. Proc Natl Acad Sci U S A. 2021;118.","DOI":"10.1073\/pnas.2012137118"},{"key":"2224_CR22","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.eplepsyres.2019.02.008","volume":"151","author":"X Hu","year":"2019","unstructured":"Hu X, Tang J, Lan X, Mi X. Increased expression of DOC2A in human and rat temporal lobe epilepsy. Epilepsy Res. 2019;151:78\u201384.","journal-title":"Epilepsy Res"},{"key":"2224_CR23","doi-asserted-by":"publisher","first-page":"4262","DOI":"10.1046\/j.1460-9568.1999.00855.x","volume":"11","author":"G Sakaguchi","year":"1999","unstructured":"Sakaguchi G, Manabe T, Kobayashi K, Orita S, Sasaki T, Naito A, et al. Doc2alpha is an activity-dependent modulator of excitatory synaptic transmission. Eur J Neurosci. 1999;11:4262\u20138.","journal-title":"Eur J Neurosci"},{"issue":"2","key":"2224_CR24","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1016\/j.cell.2019.01.048","volume":"177","author":"SB Thyme","year":"2019","unstructured":"Thyme SB, Pieper LM, Li EH, Pandey S, Wang Y, Morris NS, Sha C, Choi JW, Herrera KJ, Soucy ER, et al. Phenotypic Landscape of Schizophrenia-Associated Genes Defines Candidates and Their Shared Functions. Cell. 2019;177(2):478\u201391.","journal-title":"Cell"},{"key":"2224_CR25","doi-asserted-by":"crossref","unstructured":"Mccammon JM, Blaker-Lee A, Chen X, Sive H. The 16p11.2 homologs fam57ba and doc2a generate certain brain and body phenotypes. Hum Mol Genet. 2017;26(19):3699\u20133712.","DOI":"10.1093\/hmg\/ddx255"},{"issue":"3","key":"2224_CR26","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1111\/j.1471-4159.2006.03755.x","volume":"97","author":"AJ Groffen","year":"2006","unstructured":"Groffen AJ, Friedrich R, Brian EC, Ashery U, Verhage M. DOC2A and DOC2B are sensors for neuronal activity with unique calcium-dependent and kinetic properties. J Neurochem. 2006;97(3):818\u201333.","journal-title":"J Neurochem"},{"key":"2224_CR27","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1016\/j.neuron.2018.04.022","volume":"98","author":"NA Courtney","year":"2018","unstructured":"Courtney NA, Briguglio JS, Bradberry MM, Greer C, Chapman ER. Excitatory and Inhibitory Neurons Utilize Different Ca(2+) Sensors and Sources to Regulate Spontaneous Release. Neuron. 2018;98:977\u201391.","journal-title":"Neuron"},{"key":"2224_CR28","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1126\/science.1183765","volume":"327","author":"AJ Groffen","year":"2010","unstructured":"Groffen AJ, Martens S, Diez AR, Cornelisse LN, Lozovaya N, de Jong AP, et al. Doc2b is a high-affinity Ca2+ sensor for spontaneous neurotransmitter release. Science. 2010;327:1614\u20138.","journal-title":"Science"},{"key":"2224_CR29","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1042\/BST0380213","volume":"38","author":"S Martens","year":"2010","unstructured":"Martens S. Role of C2 domain proteins during synaptic vesicle exocytosis. Biochem Soc Trans. 2010;38:213\u20136.","journal-title":"Biochem Soc Trans"},{"key":"2224_CR30","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.tips.2013.12.002","volume":"35","author":"AV Kalueff","year":"2014","unstructured":"Kalueff AV, Stewart AM, Gerlai R. Zebrafish as an emerging model for studying complex brain disorders. Trends Pharmacol Sci. 2014;35:63\u201375.","journal-title":"Trends Pharmacol Sci"},{"key":"2224_CR31","doi-asserted-by":"crossref","unstructured":"Meshalkina DA, N KM, V KE, Collier AD, Echevarria DJ, Abreu MS et al. Zebrafish models of autism spectrum disorder. Exp Neurol. 2018;299:207\u2013216.","DOI":"10.1016\/j.expneurol.2017.02.004"},{"key":"2224_CR32","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1016\/j.neuron.2020.09.023","volume":"108","author":"B Raj","year":"2020","unstructured":"Raj B, Farrell JA, Liu J, El KJ, Carte AN, Navajas AJ, et al. Emergence of Neuronal Diversity during Vertebrate Brain Development. Neuron. 2020;108:1058\u201374.","journal-title":"Neuron"},{"key":"2224_CR33","unstructured":"Raj, B. Emergence of neuronal diversity during vertebrate brain development. Gene Expression Omnibus (GEO). https:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE158142 (2020)."},{"key":"2224_CR34","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/S0896-6273(00)81245-3","volume":"18","author":"M Verhage","year":"1997","unstructured":"Verhage M, de Vries KJ, Roshol H, Burbach JP, Gispen WH, Sudhof TC. DOC2 proteins in rat brain: complementary distribution and proposed function as vesicular adapter proteins in early stages of secretion. Neuron. 1997;18:453\u201361.","journal-title":"Neuron"},{"key":"2224_CR35","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1046\/j.1460-9568.2000.00898.x","volume":"12","author":"N Korteweg","year":"2000","unstructured":"Korteweg N, Denekamp FA, Verhage M, Burbach JP. Different spatiotemporal expression of DOC2 genes in the developing rat brain argues for an additional, nonsynaptic role of DOC2B in early development. Eur J Neurosci. 2000;12:165\u201371.","journal-title":"Eur J Neurosci"},{"key":"2224_CR36","doi-asserted-by":"publisher","first-page":"518","DOI":"10.3389\/fnhum.2018.00518","volume":"12","author":"K Ogino","year":"2018","unstructured":"Ogino K, Takahashi H, Nakamura T, Kim J, Kikuchi H, Nakahachi T, et al. Negatively Skewed Locomotor Activity Is Related to Autistic Traits and Behavioral Problems in Typically Developing Children and Those With Autism Spectrum Disorders. Front Hum Neurosci. 2018;12:518.","journal-title":"Front Hum Neurosci"},{"key":"2224_CR37","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.bbr.2011.03.025","volume":"222","author":"PJ Steenbergen","year":"2011","unstructured":"Steenbergen PJ, Richardson MK, Champagne DL. Patterns of avoidance behaviours in the light\/dark preference test in young juvenile zebrafish: a pharmacological study. Behav Brain Res. 2011;222:15\u201325.","journal-title":"Behav Brain Res"},{"key":"2224_CR38","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1080\/01677063.2017.1343827","volume":"31","author":"M Wagle","year":"2017","unstructured":"Wagle M, Nguyen J, Lee S, Zaitlen N, Guo S. Heritable natural variation of an anxiety-like behavior in larval zebrafish. J Neurogenet. 2017;31:138\u201348.","journal-title":"J Neurogenet"},{"key":"2224_CR39","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1038\/nprot.2009.225","volume":"5","author":"C Maximino","year":"2010","unstructured":"Maximino C, Marques DBT, Dias CA, Gouveia AJ, Morato S. Scototaxis as anxiety-like behavior in fish. Nat Protoc. 2010;5:209\u201316.","journal-title":"Nat Protoc"},{"key":"2224_CR40","doi-asserted-by":"publisher","first-page":"2049","DOI":"10.1007\/s00213-019-05193-4","volume":"236","author":"FJ Luchtenburg","year":"2019","unstructured":"Luchtenburg FJ, Schaaf M, Richardson MK. Functional characterization of the cannabinoid receptors 1 and 2 in zebrafish larvae using behavioral analysis. Psychopharmacology. 2019;236:2049\u201358.","journal-title":"Psychopharmacology"},{"key":"2224_CR41","doi-asserted-by":"publisher","DOI":"10.1111\/gbb.12549","volume":"18","author":"HB Lee","year":"2019","unstructured":"Lee HB, Schwab TL, Sigafoos AN, Gauerke JL, Krug RN, Serres MR, Jacobs DC, Cotter RP, Das B, Petersen MO, et al. Novel zebrafish behavioral assay to identify modifiers of the rapid, nongenomic stress response. Genes Brain Behav. 2019;18: e12549.","journal-title":"Genes Brain Behav"},{"key":"2224_CR42","doi-asserted-by":"crossref","unstructured":"Garcia-Gonzalez J, de Quadros B, Havelange W, Brock AJ, Brennan CH. Behavioral Effects of Developmental Exposure to JWH-018 in Wild-Type and Disrupted in Schizophrenia 1 (disc1) Mutant Zebrafish. Biomolecules. 2021;11.","DOI":"10.3390\/biom11020319"},{"key":"2224_CR43","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.bbr.2015.05.061","volume":"292","author":"S Shams","year":"2015","unstructured":"Shams S, Chatterjee D, Gerlai R. Chronic social isolation affects thigmotaxis and whole-brain serotonin levels in adult zebrafish. Behav Brain Res. 2015;292:283\u20137.","journal-title":"Behav Brain Res"},{"key":"2224_CR44","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.ntt.2015.11.008","volume":"53","author":"X Liu","year":"2016","unstructured":"Liu X, Lin J, Zhang Y, Peng X, Guo N, Li Q. Effects of diphenylhydantoin on locomotion and thigmotaxis of larval zebrafish. Neurotoxicol Teratol. 2016;53:41\u20137.","journal-title":"Neurotoxicol Teratol"},{"key":"2224_CR45","unstructured":"Yang, X. The brain transcriptome of widetype and doc2a\/2b knockout zebrafish. China National GeneBank DataBase (CNGBdb). https:\/\/db.cngb.org\/search\/project\/CNP0003845\/ (2022)."},{"key":"2224_CR46","first-page":"129","volume":"21","author":"NJ Kasarpalkar","year":"2014","unstructured":"Kasarpalkar NJ, Kothari ST, Dave UP. Brain-Derived Neurotrophic Factor in children with Autism Spectrum Disorder. Ann Neurosci. 2014;21:129\u201333.","journal-title":"Ann Neurosci"},{"key":"2224_CR47","doi-asserted-by":"publisher","first-page":"2297","DOI":"10.1093\/hmg\/ddr122","volume":"20","author":"A Fassio","year":"2011","unstructured":"Fassio A, Patry L, Congia S, Onofri F, Piton A, Gauthier J, et al. SYN1 loss-of-function mutations in autism and partial epilepsy cause impaired synaptic function. Hum Mol Genet. 2011;20:2297\u2013307.","journal-title":"Hum Mol Genet"},{"key":"2224_CR48","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2022.108604","volume":"129","author":"GD Mangano","year":"2022","unstructured":"Mangano GD, Riva A, Fontana A, Salpietro V, Mangano GR, Nobile G, et al. De novo GRIN2A variants associated with epilepsy and autism and literature review. Epilepsy Behav. 2022;129: 108604.","journal-title":"Epilepsy Behav"},{"key":"2224_CR49","doi-asserted-by":"publisher","first-page":"2985","DOI":"10.1038\/s41380-022-01539-1","volume":"27","author":"Y Qin","year":"2022","unstructured":"Qin Y, Du Y, Chen L, Liu Y, Xu W, Liu Y, et al. A recurrent SHANK1 mutation implicated in autism spectrum disorder causes autistic-like core behaviors in mice via downregulation of mGluR1-IP3R1-calcium signaling. Mol Psychiatry. 2022;27:2985\u201398.","journal-title":"Mol Psychiatry"},{"key":"2224_CR50","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1038\/s41593-019-0365-8","volume":"22","author":"K Zaslavsky","year":"2019","unstructured":"Zaslavsky K, Zhang WB, McCready FP, Rodrigues DC, Deneault E, Loo C, et al. SHANK2 mutations associated with autism spectrum disorder cause hyperconnectivity of human neurons. Nat Neurosci. 2019;22:556\u201364.","journal-title":"Nat Neurosci"},{"key":"2224_CR51","doi-asserted-by":"crossref","unstructured":"Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature. 2011;472:437\u2013442.sm spectrum disorder cause hyperconnectivity of human neurons. Nat Neurosci. 2019;22:556\u2013564.","DOI":"10.1038\/nature09965"},{"key":"2224_CR52","doi-asserted-by":"publisher","first-page":"1370","DOI":"10.1038\/mp.2017.144","volume":"22","author":"M Song","year":"2017","unstructured":"Song M, Martinowich K, Lee FS. BDNF at the synapse: why location matters. Mol Psychiatry. 2017;22:1370\u20135.","journal-title":"Mol Psychiatry"},{"key":"2224_CR53","doi-asserted-by":"publisher","first-page":"13773","DOI":"10.1523\/JNEUROSCI.2083-15.2015","volume":"35","author":"AL Eagle","year":"2015","unstructured":"Eagle AL, Gajewski PA, Yang M, Kechner ME, Al MB, Kennedy PJ, et al. Experience-Dependent Induction of Hippocampal DeltaFosB Controls Learning. J Neurosci. 2015;35:13773\u201383.","journal-title":"J Neurosci"},{"key":"2224_CR54","doi-asserted-by":"publisher","first-page":"4761","DOI":"10.1038\/s41467-022-32509-4","volume":"13","author":"DT Meier","year":"2022","unstructured":"Meier DT, Rachid L, Wiedemann SJ, Traub S, Trimigliozzi K, Stawiski M, et al. Prohormone convertase 1\/3 deficiency causes obesity due to impaired proinsulin processing. Nat Commun. 2022;13:4761.","journal-title":"Nat Commun"},{"key":"2224_CR55","doi-asserted-by":"crossref","unstructured":"Fetit R, Price DJ, Lawrie SM, Johnstone M. Understanding the clinical manifestations of 16p11.2 deletion syndrome: a series of developmental case reports in children. Psychiatr Genet. 2020;30:136\u2013140.","DOI":"10.1097\/YPG.0000000000000259"},{"key":"2224_CR56","doi-asserted-by":"publisher","first-page":"E5605","DOI":"10.1073\/pnas.1802104115","volume":"115","author":"R Xue","year":"2018","unstructured":"Xue R, Ruhl DA, Briguglio JS, Figueroa AG, Pearce RA, Chapman ER. Doc2-mediated superpriming supports synaptic augmentation. Proc Natl Acad Sci U S A. 2018;115:E5605\u201313.","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2224_CR57","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112243","volume":"42","author":"MH Weinschutz","year":"2023","unstructured":"Weinschutz MH, Neelakantan U, Liu Y, Fitzpatrick SE, Chen T, Wu W, et al. High-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways. Cell Rep. 2023;42: 112243.","journal-title":"Cell Rep"},{"key":"2224_CR58","doi-asserted-by":"publisher","first-page":"2424","DOI":"10.2337\/db11-1525","volume":"61","author":"L Ramalingam","year":"2012","unstructured":"Ramalingam L, Oh E, Yoder SM, Brozinick JT, Kalwat MA, Groffen AJ, et al. Doc2b is a key effector of insulin secretion and skeletal muscle insulin sensitivity. Diabetes. 2012;61:2424\u201332.","journal-title":"Diabetes"},{"key":"2224_CR59","doi-asserted-by":"publisher","first-page":"14408","DOI":"10.1038\/s41598-019-50684-1","volume":"9","author":"Q Bourgeois-Jaarsma","year":"2019","unstructured":"Bourgeois-Jaarsma Q, Verhage M, Groffen AJ. Doc2b Ca(2+) binding site mutants enhance synaptic release at rest at the expense of sustained synaptic strength. Sci Rep. 2019;9:14408.","journal-title":"Sci Rep"},{"key":"2224_CR60","doi-asserted-by":"crossref","unstructured":"Wang QW, Qin J, Chen YF, Tu Y, Xing YY, Wang Y, et al. 16p11.2 CNV gene Doc2alpha functions in neurodevelopment and social behaviors through interaction with Secretagogin. Cell Rep. 2023;42:112691.","DOI":"10.1016\/j.celrep.2023.112691"},{"issue":"3","key":"2224_CR61","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2023.112243","volume":"42","author":"MH Weinschutz","year":"2023","unstructured":"Weinschutz MH, Neelakantan U, Liu Y, Fitzpatrick SE, Chen T, Wu W, Pruitt A, Jin DS, Jamadagni P, Carlson M, et al. High-throughput functional analysis of autism genes in zebrafish identifies convergence in dopaminergic and neuroimmune pathways. Cell Rep. 2023;42(3): 112243.","journal-title":"Cell Rep"},{"key":"2224_CR62","doi-asserted-by":"publisher","first-page":"3464","DOI":"10.1038\/s41596-020-0382-9","volume":"15","author":"B Rein","year":"2020","unstructured":"Rein B, Ma K, Yan Z. A standardized social preference protocol for measuring social deficits in mouse models of autism. Nat Protoc. 2020;15:3464\u201377.","journal-title":"Nat Protoc"},{"key":"2224_CR63","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.neubiorev.2019.04.012","volume":"110","author":"T Takumi","year":"2020","unstructured":"Takumi T, Tamada K, Hatanaka F, Nakai N, Bolton PF. Behavioral neuroscience of autism. Neurosci Biobehav Rev. 2020;110:60\u201376.","journal-title":"Neurosci Biobehav Rev"},{"key":"2224_CR64","doi-asserted-by":"crossref","unstructured":"Tallafuss A, Stednitz SJ, Voeun M, Levichev A, Larsch J, Eisen J, et al. Egr1 Is Necessary for Forebrain Dopaminergic Signaling during Social Behavior. eNeuro. 2022;9.","DOI":"10.1523\/ENEURO.0035-22.2022"},{"key":"2224_CR65","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1111\/j.1601-183X.2010.00659.x","volume":"10","author":"BL Pearson","year":"2011","unstructured":"Pearson BL, Pobbe RL, Defensor EB, Oasay L, Bolivar VJ, Blanchard DC, et al. Motor and cognitive stereotypies in the BTBR T+tf\/J mouse model of autism. Genes Brain Behav. 2011;10:228\u201335.","journal-title":"Genes Brain Behav"},{"key":"2224_CR66","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.pnpbp.2014.03.007","volume":"55","author":"L Kim","year":"2014","unstructured":"Kim L, He L, Maaswinkel H, Zhu L, Sirotkin H, Weng W. Anxiety, hyperactivity and stereotypy in a zebrafish model of fragile X syndrome and autism spectrum disorder. Prog Neuropsychopharmacol Biol Psychiatry. 2014;55:40\u20139.","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"2224_CR67","doi-asserted-by":"publisher","DOI":"10.1016\/j.spen.2021.100897","volume":"38","author":"MJ McCarty","year":"2021","unstructured":"McCarty MJ, Brumback AC. Rethinking Stereotypies in Autism. Semin Pediatr Neurol. 2021;38: 100897.","journal-title":"Semin Pediatr Neurol"},{"key":"2224_CR68","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.bbr.2009.06.022","volume":"205","author":"RJ Egan","year":"2009","unstructured":"Egan RJ, Bergner CL, Hart PC, Cachat JM, Canavello PR, Elegante MF, et al. Understanding behavioral and physiological phenotypes of stress and anxiety in zebrafish. Behav Brain Res. 2009;205:38\u201344.","journal-title":"Behav Brain Res"},{"key":"2224_CR69","doi-asserted-by":"publisher","first-page":"315","DOI":"10.3390\/applbiosci1030020","volume":"1","author":"AC Wilson","year":"2022","unstructured":"Wilson AC, Rajesh KR. Habituation and behavioural response of confinement-induced anxiety conditions in a zebrafish model. Appl Biosci. 2022;1:315\u201323.","journal-title":"Appl Biosci"},{"issue":"18","key":"2224_CR70","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2221097120","volume":"120","author":"A Wang","year":"2023","unstructured":"Wang A, Wan X, Zhuang P, Jia W, Ao Y, Liu X, Tian Y, Zhu L, Huang Y, Yao J, et al. High fried food consumption impacts anxiety and depression due to lipid metabolism disturbance and neuroinflammation. P Natl Acad Sci Usa. 2023;120(18): e2073870176.","journal-title":"P Natl Acad Sci Usa"},{"key":"2224_CR71","doi-asserted-by":"publisher","DOI":"10.1111\/gbb.12459","volume":"17","author":"CE Page","year":"2018","unstructured":"Page CE, Alexander J, Shepard R, Coutellier L. Npas4 deficiency interacts with adolescent stress to disrupt prefrontal GABAergic maturation and adult cognitive flexibility. Genes Brain Behav. 2018;17: e12459.","journal-title":"Genes Brain Behav"},{"key":"2224_CR72","doi-asserted-by":"crossref","unstructured":"Rein B, Tan T, Yang F, Wang W, Williams J, Zhang F, et al. Reversal of synaptic and behavioral deficits in a 16p11.2 duplication mouse model via restoration of the GABA synapse regulator Npas4. Mol Psychiatry. 2021;26:1967\u20131979.","DOI":"10.1038\/s41380-020-0693-9"},{"key":"2224_CR73","unstructured":"Westerfield, M. The Zebrafish Book. A Guide for the Laboratory Use of Zebrafish (Danio rerio). 4th Edition, University of Oregon Press: Eugene; 2000."},{"key":"2224_CR74","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1101\/gr.248559.119","volume":"30","author":"Y Sun","year":"2019","unstructured":"Sun Y, Zhang B, Luo L, Shi DL, Wang H, Cui Z, et al. Systematic genome editing of the genes on zebrafish Chromosome 1 by CRISPR\/Cas9. Genome Res. 2019;30:118\u201326.","journal-title":"Genome Res"},{"key":"2224_CR75","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/nprot.2007.514","volume":"3","author":"C Thisse","year":"2008","unstructured":"Thisse C, Thisse B. High-resolution in situ hybridization to whole-mount zebrafish embryos. Nat Protoc. 2008;3:59\u201369.","journal-title":"Nat Protoc"},{"key":"2224_CR76","doi-asserted-by":"publisher","first-page":"D1049","DOI":"10.1093\/nar\/gkx1093","volume":"46","author":"W Pereanu","year":"2018","unstructured":"Pereanu W, Larsen EC, Das I, Estevez MA, Sarkar AA, Spring-Pearson S, et al. AutDB: a platform to decode the genetic architecture of autism. Nucleic Acids Res. 2018;46:D1049\u201354.","journal-title":"Nucleic Acids Res"},{"key":"2224_CR77","doi-asserted-by":"crossref","unstructured":"Yang C, Li J, Wu Q, Yang X, Huang AY, Zhang J, et al. AutismKB 2.0: a knowledgebase for the genetic evidence of autism spectrum disorder. Database (Oxford). 2018;2018.","DOI":"10.1093\/database\/bay106"},{"key":"2224_CR78","doi-asserted-by":"crossref","unstructured":"Abrahams BS, Arking DE, Campbell DB, Mefford HC, Morrow EM, Weiss LA, et al. SFARI Gene 2.0: a community-driven knowledgebase for the autism spectrum disorders (ASDs). Mol Autism. 2013;4:36.","DOI":"10.1186\/2040-2392-4-36"},{"key":"2224_CR79","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1016\/j.neuron.2018.01.015","volume":"97","author":"F Pamela","year":"2018","unstructured":"Pamela F, Amy MD, LeeAnne GS, Amy B, Alexies C, Amy E, et al. SPARK: A US Cohort of 50,000 Families to Accelerate Autism Research. Neuron. 2018;97:488\u201393.","journal-title":"Neuron"},{"key":"2224_CR80","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1007\/s00439-020-02199-3","volume":"139","author":"PD Stenson","year":"2020","unstructured":"Stenson PD, Mort M, Ball EV, Chapman M, Evans K, Azevedo L, et al. The Human Gene Mutation Database (HGMD((R))): optimizing its use in a clinical diagnostic or research setting. Hum Genet. 2020;139:1197\u2013207.","journal-title":"Hum Genet"},{"key":"2224_CR81","doi-asserted-by":"publisher","first-page":"3767","DOI":"10.1242\/dev.00603","volume":"130","author":"B Geldmacher-Voss","year":"2003","unstructured":"Geldmacher-Voss B, Reugels AM, Pauls S, Campos-Ortega JA. A 90-degree rotation of the mitotic spindle changes the orientation of mitoses of zebrafish neuroepithelial cells. Development. 2003;130:3767\u201380.","journal-title":"Development"},{"key":"2224_CR82","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.aquatox.2008.02.010","volume":"87","author":"CW Matson","year":"2008","unstructured":"Matson CW, Clark BW, Jenny MJ, Fleming CR, Hahn ME, Di Giulio RT. Development of the morpholino gene knockdown technique in Fundulus heteroclitus: a tool for studying molecular mechanisms in an established environmental model. Aquat Toxicol. 2008;87:289\u201395.","journal-title":"Aquat Toxicol"},{"key":"2224_CR83","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007000","volume":"13","author":"D Stainier","year":"2017","unstructured":"Stainier D, Raz E, Lawson ND, Ekker SC, Burdine RD, Eisen JS, et al. Guidelines for morpholino use in zebrafish. PLoS Genet. 2017;13: e1007000.","journal-title":"PLoS Genet"}],"container-title":["BMC Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12915-025-02224-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12915-025-02224-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12915-025-02224-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T09:04:56Z","timestamp":1751360696000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcbiol.biomedcentral.com\/articles\/10.1186\/s12915-025-02224-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,1]]},"references-count":83,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["2224"],"URL":"https:\/\/doi.org\/10.1186\/s12915-025-02224-9","relation":{},"ISSN":["1741-7007"],"issn-type":[{"value":"1741-7007","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,1]]},"assertion":[{"value":"31 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"167"}}