BRAIN EAGER: Using Optogenetic Techniques in Combination with Free Flight Perturbations to Elucidate Neural Structure Governing Flight Control in D. Melanogaster

Cornell University, Ithaca NY

Investigators

Abstract

Forging the link between individual neuron function and the behavior of collections of neurons that can produce complex behaviors is the central goal of contemporary neuroscience. The path towards achieving this goal is being revolutionized by genetic techniques that allow for manipulation of the activity of neurons and measurement of the effect on behavior. Flight behavior in the fruit fly, Drosophila, is highly suitable for this combined analysis, since flies can be genetically manipulated very easily and their rich set of free flight behaviors can be quantitatively characterized in great detail. This project will use this approach to unravel the design and operation of a remarkable neural circuit responsible for giving flies one of the fastest response times in the animal kingdom and controlling their high speed maneuvering capabilities. Using small magnets attached to the flies and applied magnetic fields, flies will be subjected to forces in midair that alter their flight. By turning on and off the neurons in the control circuit that governs their response to such forces and determining the resulting change in their wing motions, the role that each individual neuron plays in the neural circuit that governs the recovery of these insects to the experimental perturbation will be determined. More broadly this work will lay the framework for a general powerful approach for interrogating and building an understanding of many other complex neural circuits. Moreover, the discoveries made will inform design principles for the development of efficient control strategies that can be used in robots. This pipeline for discovery will be publicized through conference meetings, publications, and workshops. In addition, the analysis routines and resulting data will be made available through the Principal Investigator's group web site. The flight of fruit flies (Drosophila) provides a rich set of free flight behaviors that can be quantitatively characterized in great detail using methods recently developed by the PI. Towards this end, this project will develop a platform in which each neuron in this circuit can be manipulated using optogenetics and the altered behavioral response quantified, with the aim of dissecting with unprecedented detail a behaviorally vital yet poorly understood neural circuit. Crucially, the approach taken entails using large empirical data sets of flight kinematics in conjunction with the mathematical theory of dynamical systems to generate reduced order models. These models will be used to guide the experiment design and interpretation of the resulting kinematic data. Application of this approach to motor-neurons will be used to elucidate the role of specific steering muscles in the flight control process. Application of this approach to the inter-neurons, which relay sensory responses to the motor-neurons, is being used to elucidate the design and function of the neural control circuit that determines the fly's response to mid-air perturbations. More broadly the complexity and hierarchical layout of the machinery necessary for insect flight is typical of other complex neural circuits.