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Developmental exposure to the harmful algal bloom toxin, domoic acid (DomA), has behavioral consequences well into adulthood, but the cellular and molecular mechanisms of DomA developmental neurotoxicity are largely unknown. To assess these, we exposed zebrafish embryos to DomA during the previously identified window of susceptibility and used the well-known startle response circuit as a tool to identify specific neuronal components that are targeted by exposure to DomA. Exposure to DomA reduced startle responsiveness to both auditory\/vibrational and electrical stimuli, and even at the highest stimulus intensities tested, led to a dramatic reduction of one type of startle (short-latency c-starts). Furthermore, DomA-exposed larvae had altered kinematics for both types of startle responses tested, exhibiting shallower bend angles and slower maximal angular velocities. Using vital dye staining, immunolabeling, and live imaging of transgenic lines, we determined that although the sensory inputs were intact, the reticulospinal neurons required for short-latency c-starts were absent in most DomA-exposed larvae. Furthermore, axon tracing revealed that DomA-treated larvae also showed significantly reduced primary motor neuron axon collaterals. Overall, these results show that developmental exposure to DomA targets large reticulospinal neurons and motor neuron axon collaterals, resulting in measurable deficits in startle behavior. They further provide a framework for using the startle response circuit to identify specific neural populations disrupted by toxins or toxicants and to link these disruptions to functional consequences for neural circuit function and behavior.<\/jats:p>","DOI":"10.1093\/toxsci\/kfab066","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T15:21:40Z","timestamp":1622820100000},"page":"310-326","source":"Crossref","is-referenced-by-count":19,"title":["Developmental Exposure to Domoic Acid Disrupts Startle Response Behavior and Circuitry in Zebrafish"],"prefix":"10.1093","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3318-1883","authenticated-orcid":false,"given":"Jennifer M","family":"Panlilio","sequence":"first","affiliation":[{"name":"Biology Department, Woods Hole Oceanographic Institution, Woods Hole , Massachusetts 02543, USA"},{"name":"Massachusetts Institute of Technology (MIT) \u2013 Woods Hole Oceanographic Institution (WHOI) Joint Graduate Program in Oceanography and Oceanographic Engineering , Massachusetts 02543, USA"},{"name":"Woods Hole Center for Oceans and Human Health, Woods Hole , Massachusetts 02543, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian T","family":"Jones","sequence":"additional","affiliation":[{"name":"Biology Department, Woods Hole Oceanographic Institution, Woods Hole , Massachusetts 02543, USA"},{"name":"Massachusetts Institute of Technology (MIT) \u2013 Woods Hole Oceanographic Institution (WHOI) Joint Graduate Program in Oceanography and Oceanographic Engineering , Massachusetts 02543, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1565-5830","authenticated-orcid":false,"given":"Matthew C","family":"Salanga","sequence":"additional","affiliation":[{"name":"Biology Department, Woods Hole Oceanographic Institution, Woods Hole , Massachusetts 02543, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neelakanteswar","family":"Aluru","sequence":"additional","affiliation":[{"name":"Biology Department, Woods Hole Oceanographic Institution, Woods Hole , Massachusetts 02543, USA"},{"name":"Woods Hole Center for Oceans and Human Health, Woods Hole , Massachusetts 02543, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4358-2082","authenticated-orcid":false,"given":"Mark E","family":"Hahn","sequence":"additional","affiliation":[{"name":"Biology Department, Woods Hole Oceanographic Institution, Woods Hole , Massachusetts 02543, USA"},{"name":"Woods Hole Center for Oceans and Human Health, Woods Hole , Massachusetts 02543, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,6,7]]},"reference":[{"key":"2022060700100249900_kfab066-B1","doi-asserted-by":"crossref","first-page":"4443","DOI":"10.1242\/dev.071001","article-title":"Individual axons regulate the myelinating potential of single oligodendrocytes in vivo","volume":"138","author":"Almeida","year":"2011","journal-title":"Development"},{"key":"2022060700100249900_kfab066-B2","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1007\/BF02804901","article-title":"Harmful algal blooms and eutrophication: Nutrient sources, composition, and consequences","volume":"25","author":"Anderson","year":"2002","journal-title":"Estuaries"},{"key":"2022060700100249900_kfab066-B3"},{"key":"2022060700100249900_kfab066-B4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.hal.2018.06.001","article-title":"Pseudo-nitzschia, Nitzschia, and domoic acid: New research since 2011","volume":"79","author":"Bates","year":"2018","journal-title":"Harmful Algae"},{"key":"2022060700100249900_kfab066-B5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v032.i06","article-title":"mixtools: An R package for analyzing finite mixture models","volume":"32","author":"Benaglia","year":"2009","journal-title":"J. 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