Research

How do the nervous systems of animals integrate feedback from multiple sensory systems to coordinate robust behaviors in complex sensory landscapes? We hope to address this question by studying the sensory control of flight by Drosophila melanogaster. The agile flight behaviors exhibited by flies are achieved by a flight control system that is highly specialized to rapidly combine information from multiple sensory modalities, including vision, olfaction, audition, and several mechanosensory systems. Although the neurobiology of individual sensory systems has received much attention, the processing of multisensory information, from either an experimental or theoretical perspective, has received far less attention. The challenges of multisensory integration constrain the architecture and encoding properties of individual sensory systems; explicitly studying the integration mechanisms may be the swiftest route to advancing our understanding of the essential logic of nervous systems.

Behavioral Investigation into Multisensory Control of Flight

Behavior is inherently the outcome of integrated multisensory information, but in the lab, it is possible to stimulate individual modalities in isolation or in combination. It is also possible to arrange experimental conditions that only rarely emerge in natural flight. In particular, we can study the behavioral response to conflicting cues, such as a visual stimulus corresponding to straight flight, and a simultaneous crosswind. Even with great care, investigations into the neural circuitry underlying multisensory integration can suffer from combinatorial explosion-all potentially relevant stimuli for each sensory system should be tested against relevant stimuli for all other systems. For this reason, we exploit quantitative behavior as the necessary, expeditious tool for establishing an algorithmic basis for the multisensory process, for which the contributing neuronal circuitry can be subsequently identified.

The fly's nervous system must solve a challenging inference problem-self-generated motion in varying landscapes combined with shifting winds generates a confounding and potentially ambiguous sensory percept. For this reason it is essential that the fly's nervous system makes use of information from multiple sensory systems. We hope to disentangle the contributions of visual, wind, and inertial sensing to the flight control system of Drosophila using a variety of tethered flight experiments. In the virtual-reality flight simulators, tethered flies are held stationary while flying, and motion is simulated by dynamically updating a panoramic visual display. To study sensory systems that are ideally stimulated only when the fly is in motion, we use a robotic system for moving a tethered fly in a controlled manner. We also make use of computational models of the behavioral responses of flies to provide a necessary context for investigations into the supporting neural architecture.

Investigation of Neuronal Circuits Underlying Multisensory Processing

Our approach is to start with behavioral assays targeted to address specific biological questions. One we have identified and characterized examples of multisensory fusion in wild-type flies, we will then use the molecular tools that are available for Drosophila to pursue the neuronal circuits underlying these behaviors. By combining detailed single fly behavioral measurements with the expression control provided by the GAL4-UAS system, we can begin to examine the role of specific brain regions in candidate behaviors. One line of work will use genetically encoded optical reporters, such as those that measure intracellular calcium, to localize the integration of sensory information to specific brain regions. Another promising avenue for the study of brain circuitry in intact animals is the use of optically gated ion channels to activate or inhibit specific neurons in candidate regions. The ability to regulate neural activity in behaving flies will go a long way toward identifying the components of the circuitry that implement the sensor fusion process that generates robust flight control in flies.

I do not expect any single method to provide a magic bullet for elucidating structure-function relationships in the brain; a coordinated and collaborative effort that utilizes multiple strategies will be critical. The Janelia Farm Research campus is an ideal place to make use of both top-down (behavior) and bottom-up (imaging/genetics) approaches, combined with computational modeling, to study sensory fusion in Drosophila.

Development of Modular Visual Stimuli

An understanding of fly behavior requires a variety of experimental methods; the design of laboratory instruments is a large part of what we do. I designed a modular electronic display system for virtual-reality simulators of fly flight. The flexibility of these displays makes it possible to combine a visual stimulus with any tethered fly experiment. The software components and hardware plans for this project are available online HERE. I plan to continue to develop this system and to support the growing community of users.

System Theory Applications in Behavior

An ongoing effort in our lab will be to use the tools of system theory to understand Drosophila flight behavior. This effort will include studying the role of feedback in flight and using system identification methods to develop models of biological systems. Applying a systems perspective to the study of the neural control of fly behavior will be mutually beneficial: theory-inspired considerations motivate further experiments, and a study of the architecture of insect nervous systems may reveal fruitful theoretic problems that are unresolved.