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Pharmaceutical and Parametric Modulation of Prepulse Inhibition in Danio Rerio

Abstract

Pre-pulse inhibition is a sensorimotor gating phenomenon that allows an organism to react differentially to stimuli based on prior sub-threshold exposure, allowing the organism to ignore unnecessary cues.

While PPI is well-documented in mammals, work on zebrafish has been much more limited. Previous work demonstrated PPI in zebrafish, but the mechanisms underlying the behavior are not well understood.

Many circuit-based models have been suggested to explain PPI in mammalian systems, however, the complexity of the mammalian brains makes these ideas difficult to test. Despite the problems inherent in using a developmentally immature model, such as larval zebrafish, for PPI, the neural circuit mediating startle in the zebrafish is well defined which facilitates an understanding of PPI within a discrete neural circuit.

We manipulated several variables to determine the optimal parameters for pharmacological testing of PPI: 1) prepulse length, 2) interval length, 3) prepulse volume, 4) startle volume, 5) fish grouping and 6) fish age, and 7) well size. We also used pharmacological agents to dissect the roles of N-methyl d-aspartate, dopamine, and serotonin receptors in PPI.

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