Studying Behavior and Neuronal Circuit Mechanisms Underlying Anxiety in Zebrafish Brain.

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In the proposed project, we will study the behavior underlying anxiety in zebrafish and how different brain areas contribute to the sensation of anxiety. To achieve this goal we will combine behavioral assays and non-invasive brain imaging tools with the vast genetic toolkit applicable to zebrafish. These methods will allow us to study anxiety-like behavior in zebrafish models and to simultaneously monitor or perturb the activity of brain regions associated with anxiety such as the amygdala, the hippocampus and the habenula. We expect to perform our experiments in approximately 920 zebrafish between 4 and 6 weeks post fertilization.
None of our experiments involves chronic or acute pain or invasive surgery and all experiments are designed to be non-invasive. Our animals’ health is of major importance for all our behavioral and imaging experiments. During our behavioral experiments, zebrafish will be exposed to given concentrations of a selected number of pharmaceuticals. All pharmaceuticals we use are listed below. The concentrations we use follow the disposable literature about these pharmaceuticals and the recommendations of the manufacturers. None of the concentrations and exposure times we use will intoxicate or lethally poison our fish.
Using a small vertebrate such as zebrafish, we replace mammalian animal models such as mice or rats. Moreover, we refine the exposure time and the concentrations of the pharmaceuticals we use in order to reduce it to a minimum and to expose our fish to the least effective dose possible. All our experiments require working with living animals since we aim at studying sensations and behaviors of species that are only present in living species. As soon as a sufficient extent of information will be gathered, our experiments will allow us to design computational models of brain circuits underlying basic processes such as anxiety.
We anticipate that our results will go beyond zebrafish and will inspire fellow colleagues of ours not only to stimulate brain circuits digitally but also to comprehend the neural mechanisms underlying debilitating psychological diseases such as major depressive disorder or general anxiety disorder that rank among the most common psychiatric disorders worldwide.