Zebrafish model for behavioural screening of neuroactive substances

Research proposed here aims to develop a zebrafish model for examining behavioural indicators of neuralfunction that can be incorporated into screens for gene actions, environmental toxins, and drugs. The partnercompany is DMF Medical Inc, a Nova Scotia based corporation dedicated to research leading to improvedoutcomes following anesthesia and the company is interested in this project as a means of understanding themechanisms underlying detrimental post-operative side effects of commonly used anaesthetics. The firstproject will involve the use of measurements of behavioural parameters (movements, posture, responsiveness)to characterize the acute effects of sevoflurane, desflurane and isoflurane and determine dose-response curvesand recovery periods in zebrafish. The second project will involve the development of learning paradigmssuitable for testing long-term effects of anaesthetics on cognitive functions. Our lab already established anolfactory conditioning paradigm for zebrafish and we will compare this paradigm to ones involving vision andhearing to provide a robust and efficient screening procedure which is optimized for zebrafish. The thirdproject will then involve the examination of anaesthetic-induced cognitive deficits. Specifically, we willconduct pilot studies to examine the long-term effects of anaesthetics on the abilities of fish to form and retainmemories associated with the learning paradigms. By providing novel screening procedures for neurotoxiceffects of anaesthetics and/or their metabolites, the project will facilitate the company's goal of improvinganesthesia technology, but the work will also offer a basis for the development of screening procedures forbroader classes of drugs and/or genetic manipulations which affect behaviour and learning and thereby shedlight on underlying neural mechanisms. Future screens for environmental toxins based on these procedures willalso provide a better understanding of the effects of anthropogenic chemicals being introduced into aquaticecosystems. Finally, by funding several students and recent graduates the project will also benefit our nextgeneration of research scientists by engaging them in meaningful research.