{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T22:31:18Z","timestamp":1772231478554,"version":"3.50.1"},"reference-count":86,"publisher":"Society for Neuroscience","issue":"31","license":[{"start":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T00:00:00Z","timestamp":1738281600000},"content-version":"vor","delay-in-days":210,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["NS117886"],"award-info":[{"award-number":["NS117886"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["NS122191"],"award-info":[{"award-number":["NS122191"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"accepted":{"date-parts":[[2024,6,27]]},"published-print":{"date-parts":[[2024,7,31]]},"abstract":"<jats:p>\n                    Although hyperactivity is associated with a wide variety of neurodevelopmental disorders, the early embryonic origins of locomotion have hindered investigation of pathogenesis of these debilitating behaviors. The earliest motor output in vertebrate animals is generated by clusters of early-born motor neurons (MNs) that occupy distinct regions of the spinal cord, innervating stereotyped muscle groups. Gap junction electrical synapses drive early spontaneous behavior in zebrafish, prior to the emergence of chemical neurotransmitter networks. We use a genetic model of hyperactivity to gain critical insight into the consequences of errors in motor circuit formation and function, finding that Fragile X syndrome model mutant zebrafish are hyperexcitable from the earliest phases of spontaneous behavior, show altered sensitivity to blockade of electrical gap junctions, and have increased expression of the gap junction protein Connexin 34\/35. We further show that this hyperexcitable behavior can be rescued by pharmacological inhibition of electrical synapses. We also use functional imaging to examine MN and interneuron (IN) activity in early embryogenesis, finding genetic disruption of electrical gap junctions uncouples activity between\n                    <jats:italic>mnx1<\/jats:italic>\n                    <jats:sup>+<\/jats:sup>\n                    MNs and INs. Taken together, our work highlights the importance of electrical synapses in motor development and suggests that the origins of hyperactivity in neurodevelopmental disorders may be established during the initial formation of locomotive circuits.\n                  <\/jats:p>","DOI":"10.1523\/jneurosci.2275-23.2024","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T13:50:26Z","timestamp":1720187426000},"page":"e2275232024","source":"Crossref","is-referenced-by-count":3,"title":["Electrical Synapses Mediate Embryonic Hyperactivity in a Zebrafish Model of Fragile X Syndrome"],"prefix":"10.1523","volume":"44","author":[{"given":"Kaleb D.","family":"Miles","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3329-5370","authenticated-orcid":false,"given":"Chase M.","family":"Barker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristen P.","family":"Russell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4500-0672","authenticated-orcid":false,"given":"Bruce H.","family":"Appel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2109-2448","authenticated-orcid":false,"given":"Caleb A.","family":"Doll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"393","published-online":{"date-parts":[[2024,7,5]]},"reference":[{"key":"2025111207300738000_44.31.e2275232024.1","doi-asserted-by":"crossref","first-page":"e103751","DOI":"10.1371\/journal.pone.0103751","article-title":"Anaesthetic tricaine acts preferentially on neural voltage-gated sodium channels and fails to block directly evoked muscle contraction","volume":"9","author":"Attili","year":"2014","journal-title":"PLoS One"},{"key":"2025111207300738000_44.31.e2275232024.2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1245629"},{"key":"2025111207300738000_44.31.e2275232024.3","doi-asserted-by":"crossref","first-page":"962901","DOI":"10.3389\/fnins.2022.962901","article-title":"Fmrp regulates neuronal balance in embryonic motor circuit formation","volume":"16","author":"Barker","year":"2022","journal-title":"Front Neurosci"},{"key":"2025111207300738000_44.31.e2275232024.4","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903020315"},{"key":"2025111207300738000_44.31.e2275232024.5","doi-asserted-by":"publisher","DOI":"10.1017\/S0012162201002833"},{"key":"2025111207300738000_44.31.e2275232024.6","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e3180ca9a9a"},{"key":"2025111207300738000_44.31.e2275232024.7","doi-asserted-by":"crossref","first-page":"587978","DOI":"10.3389\/fnmol.2020.587978","article-title":"Effects of constitutive and acute connexin 36 deficiency on brain-wide susceptibility to PTZ-induced neuronal hyperactivity","volume":"13","author":"Brunal","year":"2021","journal-title":"Front Mol Neurosci"},{"key":"2025111207300738000_44.31.e2275232024.8","doi-asserted-by":"publisher","DOI":"10.1021\/jm00268a011"},{"key":"2025111207300738000_44.31.e2275232024.9","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.47837"},{"key":"2025111207300738000_44.31.e2275232024.10","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.753274"},{"key":"2025111207300738000_44.31.e2275232024.11","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2020.00025"},{"key":"2025111207300738000_44.31.e2275232024.12","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-020-00706-1"},{"key":"2025111207300738000_44.31.e2275232024.13","doi-asserted-by":"publisher","DOI":"10.3171\/jns.2006.105.1.77"},{"key":"2025111207300738000_44.31.e2275232024.14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007910"},{"key":"2025111207300738000_44.31.e2275232024.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.06.046"},{"key":"2025111207300738000_44.31.e2275232024.16","doi-asserted-by":"publisher","DOI":"10.1002\/neu.20226"},{"key":"2025111207300738000_44.31.e2275232024.17","doi-asserted-by":"publisher","DOI":"10.1242\/dev.113.supplement_2.141"},{"key":"2025111207300738000_44.31.e2275232024.18","doi-asserted-by":"publisher","DOI":"10.1002\/syn.20519"},{"key":"2025111207300738000_44.31.e2275232024.19","doi-asserted-by":"publisher","DOI":"10.1242\/dev.02044"},{"key":"2025111207300738000_44.31.e2275232024.20","doi-asserted-by":"publisher","DOI":"10.1242\/dev.123.1.399"},{"key":"2025111207300738000_44.31.e2275232024.21","doi-asserted-by":"publisher","DOI":"10.1016\/0012-1606(88)90245-X"},{"key":"2025111207300738000_44.31.e2275232024.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2007.06.021"},{"key":"2025111207300738000_44.31.e2275232024.23","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.308205"},{"key":"2025111207300738000_44.31.e2275232024.24","doi-asserted-by":"publisher","DOI":"10.1007\/s10519-020-09995-7"},{"key":"2025111207300738000_44.31.e2275232024.25","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.122205699"},{"key":"2025111207300738000_44.31.e2275232024.26","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-020-0654-2"},{"key":"2025111207300738000_44.31.e2275232024.27","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aai8133"},{"key":"2025111207300738000_44.31.e2275232024.28","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.pnpbp.2014.03.007","article-title":"Anxiety, hyperactivity and stereotypy in a zebrafish model of fragile X syndrome and autism spectrum disorder","volume":"55","author":"Kim","year":"2014","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"2025111207300738000_44.31.e2275232024.29","doi-asserted-by":"publisher","DOI":"10.1002\/aja.1002030302"},{"key":"2025111207300738000_44.31.e2275232024.30","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2013.00172"},{"key":"2025111207300738000_44.31.e2275232024.31","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903020316"},{"key":"2025111207300738000_44.31.e2275232024.32","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1978.sp012545"},{"key":"2025111207300738000_44.31.e2275232024.33","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.66898"},{"key":"2025111207300738000_44.31.e2275232024.34","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22-24-10898.2002"},{"key":"2025111207300738000_44.31.e2275232024.35","doi-asserted-by":"crossref","first-page":"jkac062","DOI":"10.1093\/g3journal\/jkac062","article-title":"Connexinplexity: the spatial and temporal expression of connexin genes during vertebrate organogenesis","volume":"12","author":"Lukowicz-Bedford","year":"2022","journal-title":"G3"},{"key":"2025111207300738000_44.31.e2275232024.36","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0808946106"},{"key":"2025111207300738000_44.31.e2275232024.37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2017.10.011"},{"key":"2025111207300738000_44.31.e2275232024.38","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4587-13.2014"},{"key":"2025111207300738000_44.31.e2275232024.39","doi-asserted-by":"publisher","DOI":"10.1038\/nature05588"},{"key":"2025111207300738000_44.31.e2275232024.40","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2225"},{"key":"2025111207300738000_44.31.e2275232024.41","doi-asserted-by":"publisher","DOI":"10.1002\/cne.902510204"},{"key":"2025111207300738000_44.31.e2275232024.42","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.028159"},{"key":"2025111207300738000_44.31.e2275232024.43","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2014.12.001"},{"key":"2025111207300738000_44.31.e2275232024.44","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.25364"},{"key":"2025111207300738000_44.31.e2275232024.45","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1405253111"},{"key":"2025111207300738000_44.31.e2275232024.46","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1749-8104-9-19","article-title":"Spinal neurons require Islet1 for subtype-specific differentiation of electrical excitability","volume":"9","author":"Moreno","year":"2014","journal-title":"Neural Dev"},{"key":"2025111207300738000_44.31.e2275232024.47","doi-asserted-by":"publisher","DOI":"10.1007\/s11920-010-0145-3"},{"key":"2025111207300738000_44.31.e2275232024.48","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1000887108"},{"key":"2025111207300738000_44.31.e2275232024.49","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.06-08-02278.1986"},{"key":"2025111207300738000_44.31.e2275232024.50","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4886(91)90007-Y"},{"key":"2025111207300738000_44.31.e2275232024.51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051456"},{"key":"2025111207300738000_44.31.e2275232024.52","doi-asserted-by":"publisher","DOI":"10.1111\/jir.12234"},{"key":"2025111207300738000_44.31.e2275232024.53","doi-asserted-by":"publisher","DOI":"10.1159\/000329420"},{"key":"2025111207300738000_44.31.e2275232024.54","doi-asserted-by":"publisher","DOI":"10.1242\/dev.01456"},{"key":"2025111207300738000_44.31.e2275232024.55","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2015.01.020"},{"key":"2025111207300738000_44.31.e2275232024.56","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.10390"},{"key":"2025111207300738000_44.31.e2275232024.57","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.12261"},{"key":"2025111207300738000_44.31.e2275232024.58","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0703357104"},{"key":"2025111207300738000_44.31.e2275232024.59","doi-asserted-by":"crossref","first-page":"108991","DOI":"10.1016\/j.celrep.2021.108991","article-title":"Cell-type-specific profiling of human cellular models of fragile X syndrome reveal PI3K-dependent defects in translation and neurogenesis","volume":"35","author":"Raj","year":"2021","journal-title":"Cell Rep"},{"key":"2025111207300738000_44.31.e2275232024.60","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4695(199812)37:4<622::AID-NEU10>3.0.CO;2-S"},{"key":"2025111207300738000_44.31.e2275232024.61","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-11-03964.2000"},{"key":"2025111207300738000_44.31.e2275232024.62","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)00416-0"},{"key":"2025111207300738000_44.31.e2275232024.63","doi-asserted-by":"publisher","DOI":"10.1186\/s11689-017-9184-y"},{"key":"2025111207300738000_44.31.e2275232024.64","doi-asserted-by":"publisher","DOI":"10.1186\/1749-8104-7-35"},{"key":"2025111207300738000_44.31.e2275232024.65","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3360"},{"key":"2025111207300738000_44.31.e2275232024.66","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.02.076"},{"key":"2025111207300738000_44.31.e2275232024.67","doi-asserted-by":"crossref","first-page":"e68124","DOI":"10.7554\/eLife.68124","article-title":"Gjd2b-mediated gap junctions promote glutamatergic synapse formation and dendritic elaboration in Purkinje neurons","volume":"10","author":"Sitaraman","year":"2021","journal-title":"Elife"},{"key":"2025111207300738000_44.31.e2275232024.68","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.1002\/ajmg.a.31388","article-title":"ADHD symptoms in children with FXS","volume":"140","author":"Sullivan","year":"2006","journal-title":"Am J Med Genet Part A"},{"key":"2025111207300738000_44.31.e2275232024.69","doi-asserted-by":"crossref","first-page":"461","DOI":"10.3109\/01480545.2013.776582","article-title":"Retinal toxicity associated with high dose of meclofenamic acid","volume":"36","author":"Sun","year":"2013","journal-title":"Drug Chem Toxicol"},{"key":"2025111207300738000_44.31.e2275232024.70","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2331-10.2010"},{"key":"2025111207300738000_44.31.e2275232024.71","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2336265100"},{"key":"2025111207300738000_44.31.e2275232024.72","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2012.10.025"},{"key":"2025111207300738000_44.31.e2275232024.73","doi-asserted-by":"publisher","DOI":"10.1046\/j.1528-1157.2001.26900.x"},{"key":"2025111207300738000_44.31.e2275232024.74","doi-asserted-by":"publisher","DOI":"10.1038\/75768"},{"key":"2025111207300738000_44.31.e2275232024.75","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0019683"},{"key":"2025111207300738000_44.31.e2275232024.76","doi-asserted-by":"publisher","DOI":"10.1242\/jeb.205.6.711"},{"key":"2025111207300738000_44.31.e2275232024.77","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90397-H"},{"key":"2025111207300738000_44.31.e2275232024.78","doi-asserted-by":"publisher","DOI":"10.3791\/61564"},{"key":"2025111207300738000_44.31.e2275232024.79","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.08.039"},{"key":"2025111207300738000_44.31.e2275232024.80","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2011.12.002"},{"key":"2025111207300738000_44.31.e2275232024.81","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2001.86.3.1481"},{"key":"2025111207300738000_44.31.e2275232024.82","doi-asserted-by":"crossref","first-page":"e53968","DOI":"10.7554\/eLife.53968","article-title":"Efficient targeted integration directed by short homology in zebrafish and mammalian cells","volume":"9","author":"Wierson","year":"2020","journal-title":"Elife"},{"key":"2025111207300738000_44.31.e2275232024.83","doi-asserted-by":"publisher","DOI":"10.1038\/nature10958"},{"key":"2025111207300738000_44.31.e2275232024.84","doi-asserted-by":"crossref","first-page":"368","DOI":"10.3389\/fnmol.2017.00368","article-title":"Combination therapy in fragile x syndrome; possibilities and pitfalls illustrated by targeting the mGluR5 and GABA pathway simultaneously","volume":"10","author":"Zeidler","year":"2017","journal-title":"Front Mol Neurosci"},{"key":"2025111207300738000_44.31.e2275232024.85","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20766"},{"key":"2025111207300738000_44.31.e2275232024.86","doi-asserted-by":"publisher","DOI":"10.1177\/1073858410386384"}],"container-title":["The Journal of Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.2275-23.2024","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1523\/JNEUROSCI.2275-23.2024","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T15:30:44Z","timestamp":1762961444000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jneurosci.org\/lookup\/doi\/10.1523\/JNEUROSCI.2275-23.2024"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,5]]},"references-count":86,"journal-issue":{"issue":"31","published-online":{"date-parts":[[2024,7,31]]},"published-print":{"date-parts":[[2024,7,31]]}},"alternative-id":["10.1523\/JNEUROSCI.2275-23.2024"],"URL":"https:\/\/doi.org\/10.1523\/jneurosci.2275-23.2024","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.08.25.554828","asserted-by":"object"}]},"ISSN":["0270-6474","1529-2401"],"issn-type":[{"value":"0270-6474","type":"print"},{"value":"1529-2401","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,5]]}}}