The cellular and molecular basis of motion computations

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How neural networks perform many critical computations is not understood. In sensory systems, a variety of computations extract salient information from the environment and guide appropriate behavior. Despite decades of work, our understanding of these processes remains fragmentary: in some systems, specific neurons have been identified that respond to distinct sensory cues; in others, specific behavioral outputs or computational models that predict physiology or behavior are known. However, a complete understanding of how neurons gain specific physiological properties, how they are organized in circuits and how these circuits guide distinct behaviors, has not been established in any system. A comprehensive understanding of brain function at all levels will open up new avenues for treating psychiatric or neurological diseases.Animals ranging from insects to humans use visual information, especially motion cues, to navigate through the environment, capture prey, or escape predators. Because motion vision requires circuits to integrate visual information over both space and time it has long been considered a paradigmatic computation for understanding brain function. Computational models that describe how motion information can be extracted have existed for more than 50 years, and explain motion perception from flies to humans. However, the neural circuits that implement these models remain largely unknown. Moreover, many molecular and cellular mechanisms regulate synaptic activity or modulate cellular properties in identified neurons, but they have only rarely been associated with specific, behaviorally relevant computations. While the goal should be to link such mechanisms to the ultimate read-out, animal behavior, this is impossible in many systems. I intend to achieve this by studying motion detection in a genetic model organism, the fruit fly Drosophila. In flies, motion-guided behaviors have been studied in detail and described computationally. I propose cell biological and genetic approaches to manipulate critical neurons in motion detecting circuits. In combination with physiology and quantitative behavioral analysis, these studies will identify the cellular and molecular mechanisms that guide behavioral responses to motion. I will then apply a powerful genetic toolkit I have built to manipulate neuronal function in specific neurons, thereby identifying the circuits that underlie specific motion computations. Finally, I will define the response space of a large class of visual system neurons and identify their function in processing streams.In summary, this project will provide an integrated understanding of a paradigmatic neural computation that links molecular mechanisms to a defined circuit and to motor output. This work will identify general mechanisms by which a nervous system can vertically integrate molecular, cellular and circuit mechanisms to compute behaviorally critical outputs from specific inputs.