Developmental and functional analysis of neural circuits controlling navigation in Drosophila

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Summary One of the most pressing research goals in neurobiology is to understand how brain circuits develop, and how these circuits control the behavior of an animal. This problem is of general importance if one wants to understand, and (therapeutically) manipulate, brain circuitry in a medical setting. A prerequisite to attain this goal is (1) the detailed mapping of complete neuron assemblies that embody specific circuits, and (2) the availability of precision tools for functional studies. Both of these conditions are now met for Drosophila. Complete connectomes (digital maps that contain all brain neurons and their synaptic connections) exist for both the larval stage (funded in part by this grant in previous years) and the adult. And in addition, genetic tools have been developed that allow one to manipulate (that is, silence, or activate) virtually every neuron, or at least neuron class, and test for the effect on specific behaviors that one is interested in. The strategy then is to extract from the connectome a wiring diagram of a specific circuit, develop hypotheses of how the different elements in the circuit interact, and use genetic tools to test these hypotheses. Studies of this proposal focus on a Drosophila brain circuit involved in navigation. Animals navigate in response to sensory stimuli in order to find food and mating partners, or avoid danger. Brain centers controlling navigation require processed, multimodal sensory input (smells, visual cues) which are integrated with proprioceptive input (feed back from muscles, joints etc) to calculate the commands required to steer the animal in the right direction. Our analysis of the larval connectome highlights a brain center called the lateral accessory lobe (LAL) as a focus of interest. We have identified the relevant LAL neuron classes and their connections, and are in the process to systematically screen for genetic constructs with which we can target these neuron classes to do functional studies. Larvae have a simple, highly quantifiable navigation behavior that allows them to find a food source (by odor) or avoid light. We will analyze how the LAL controls motor circuits that carry out this behavior. The second and third objective of the proposal is to study how the larval LAL neurons become modified and incorporated in the LAL of the adult. Adult flies have a new set of organs (e.g., wings, legs) with which to move, and receptors with which to sense; but according to our initial data, the larval neurons remain and have to adapt to cope with their new input and output. Using the connectome of the adult brain and our genetic tools we intend to identify the descendants of larval neurons in the LAL, and to address their function in adult navigation.