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Hillman, C.

Publications and source records attributed to Hillman, C..

2 recordsLinked to original sources

Evaluating anaesthetics for improving scientific research and welfare using larval zebrafish

Establishing anaesthesia for ensuring both animal welfare and compatibility with protocols required for different areas of scientific research is vital. Zebrafish (Danio rerio) are one of the most used animal models in research; however, little is known about the appropriateness of anaesthetic used for this species, especially for embryo-larval life stages. Using a combination of whole-brain functional imaging, quantification of cardiovascular performance, and behaviour, we explore the efficacy and tolerability of six widely used fish anaesthetics (2-phenoxyethanol, benzocaine, etomidate, MS222, isoeugenol and quinaldine sulfate) in larval zebrafish. We show that MS222 and quinaldine sulfate are the most suitable for achieving deep anaesthesia, while etomidate is better suited for studies focused on the cardiovascular system. Only quinaldine sulfate was found to be aversive. Our findings aid researchers for selecting the most suitable anaesthetic compounds and concentrations for their specific research goals, and the refinement of studies using anaesthesia in larval zebrafish.

physiology↗

adgrl3.1-deficient zebrafish show noradrenaline-mediated externalizing behaviors, and altered expression of externalizing disorder-candidate genes, suggesting functional targets for treatment

Externalising disorders (ED) are a cause of concern for public health, and their high heritability make genetic risk factors a priority for research. Adhesion G Protein-Coupled Receptor L3 (ADGRL3) is strongly linked to several EDs, and loss-of-function models have shown impacts of this gene on several core ED-related behaviors. For example, adgrl3.1-/- zebrafish show high levels of hyperactivity. However, our understanding of the mechanisms by which this gene influences behavior is incomplete. Here we characterized, for the first time, externalizing behavioral phenotypes of adgrl3.1-/- zebrafish and found them to be highly impulsive, show boldness in a novel environment, have attentional deficits, and show high levels of hyperactivity. All of these phenotypes were rescued by atomoxetine, demonstrating noradrenergic mediation of the externalizing effects of adgrl3.1. Transcriptomic analyses of the brains of adgrl3.1-/- vs wild type fish revealed several differentially expressed genes and enriched gene clusters that were independent of noradrenergic manipulation. This suggests new putative functional pathways underlying ED-related behaviors, and potential targets for the treatment of ED.

neuroscience↗