A fundamental goal of neuroscience is to understand how information processing in neural circuits gives rise to behavior. Even the simplest actions can involve hundreds of neurons distributed throughout the brain. However, for most behaviors, little is known about which neurons play an important role, how they are organized into circuits, or how activity is transformed between different brain areas. The zebrafish model provides a unique opportunity to thoroughly dissect the neural basis of behavior in a vertebrate, due to their small, transparent brains, robust visual responses, and amenability to genetic manipulation. Using two-photon imaging, we can scan the entire area of the brain while monitoring the activity of individual neurons. This research programme aims to dissect the circuits underlying simple visually guided behaviors in larval zebrafish using a combination of state-of-the-art imaging, genetics and behavioral analysis. We propose to 1) perform a quantitative analysis of zebrafish behavior using high speed videography, and a custom designed arena for presentation of visual stimuli to freely swimming fish, 2) identify individual neurons and circuits that are active during these behaviors using two-photon imaging of fish expressing genetically encoded calcium indicators to and 3) perturb activity in these circuits using targeted single cell laser ablations and optogenetics. These experiments will map out the functional architecture of the zebrafish brain, revealing sets of neurons that comprise complete behavioral circuits in a vertebrate. Furthermore, they will provide an essential framework for the analysis of neural development, genetic mutants and disease models.
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