Publication Date:
2022-06-07
Description:
Author Posting. © The Author(s), 2021. This is the author's version of the work. It is posted here by permission of Oxford University Press for personal use, not for redistribution. The definitive version was published in Toxicological Sciences 182(20), (2021): 310-326, https://doi.org/10.1093/toxsci/kfab066.
Description:
Harmful algal blooms produce potent neurotoxins that accumulate in seafood and are hazardous to human health. 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.
Description:
This research was supported by a WHOI Von Damm and Ocean Ridge Initiative Fellowships to J.M.P. and the Woods Hole Center for Oceans and Human Health (NIH: P01ES021923 and P01ES028938; NSF: OCE-1314642 and OCE-1840381).
Description:
2022-06-07
Keywords:
domoic acid
;
harmful algal blooms
;
harmful algal bloom toxins
;
developmental toxicity
;
startle response
;
escape response
;
startle circuit
Repository Name:
Woods Hole Open Access Server
Type:
Preprint
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