{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:43:36Z","timestamp":1791409416544,"version":"4.3.3"},"reference-count":49,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,8,3]],"date-time":"2015-08-03T00:00:00Z","timestamp":1438560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["121795"],"award-info":[{"award-number":["121795"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2015,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>To determine the impact of a controlled loss of dopaminergic neurons on locomotor function, we generated transgenic zebrafish, Tg(<jats:italic>dat<\/jats:italic>:<jats:italic><jats:styled-content style=\"fixed-case\">CFP<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">NTR<\/jats:styled-content><\/jats:italic>), expressing a cyan fluorescent protein\u2010nitroreductase fusion protein (<jats:styled-content style=\"fixed-case\">CFP<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">NTR<\/jats:styled-content>) under the control of <jats:italic>dopamine transporter<\/jats:italic> (<jats:italic>dat<\/jats:italic>) <jats:italic>cis<\/jats:italic>\u2010regulatory elements. Embryonic and larval zebrafish express the transgene in several groups of dopaminergic neurons, notably in the olfactory bulb, telencephalon, diencephalon and caudal hypothalamus. Administration of the pro\u2010drug metronidazole (Mtz) resulted in activation of caspase 3 in <jats:styled-content style=\"fixed-case\">CFP<\/jats:styled-content>\u2010positive neurons and in a reduction in <jats:italic>dat<\/jats:italic>\u2010positive cells by 5\u00a0days post\u2010fertilization (dpf). Loss of neurons coincided with impairments in global locomotor parameters such as swimming distance, percentage of time spent moving, as well as changes in tail bend parameters such as time to maximal bend and angular velocity. Dopamine levels were transiently decreased following Mtz administration. Recovery of some of the locomotor parameters was observed by 7 dpf. However, the total numbers of <jats:italic>dat<\/jats:italic>\u2010expressing neurons were still decreased at 7, 12, or 14 dpf, even though there was evidence for production of new <jats:italic>dat<\/jats:italic>\u2010expressing cells. Tg(<jats:italic>dat<\/jats:italic>:<jats:italic><jats:styled-content style=\"fixed-case\">CFP<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">NTR<\/jats:styled-content><\/jats:italic>) zebrafish provide a model to correlate altered dopaminergic neuron numbers with locomotor function and to investigate factors influencing regeneration of dopaminergic neurons.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13214-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nWe have generated transgenic zebrafish expressing nitroreductase for the conditional and specific ablation of dopaminergic (DA) neurons in the larval zebrafish brain. We are able to induce a persistent reduction in DA neurons with transient locomotor impairments. Our transgenic zebrafish offer a model for understanding the impact of altered DA neuron populations on larval locomotor function and for the study of dopamine neuron regeneration following tissue specific ablation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13214","type":"journal-article","created":{"date-parts":[[2015,6,27]],"date-time":"2015-06-27T05:49:12Z","timestamp":1435384152000},"page":"249-260","source":"Crossref","is-referenced-by-count":59,"title":["Chemogenetic ablation of dopaminergic neurons leads to transient locomotor impairments in zebrafish larvae"],"prefix":"10.1111","volume":"135","author":[{"given":"Rafael","family":"Godoy","sequence":"first","affiliation":[{"name":"Center for Advanced Research in Environmental Genomics Department of Biology University of Ottawa Ottawa K1N\u20106N5 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Noble","sequence":"additional","affiliation":[{"name":"Center for Advanced Research in 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