Optogenetics seminars

The ability to keep track of one’s location in space is a critical behavior for animals navigating to and from a salient location, and its computational basis is now beginning to be unraveled. Here, we tracked flies in a ring-shaped channel as they executed bouts of search triggered by optogenetic activation of sugar receptors. Unlike experiments in open field arenas, which produce highly tortuous search trajectories, our geometrically constrained paradigm enabled us to monitor flies’ decisions to move toward or away from the fictive food. Our results suggest that flies use path integration to remember the location of a food site even after it has disappeared, and flies can remember the location of a former food site even after walking around the arena one or more times. To determine the behavioral algorithms underlying Drosophila search, we developed multiple state transition models and found that flies likely accomplish path integration by combining odometry and compass navigation to keep track of their position relative to the fictive food. Our results indicate that whereas flies re-zero their path integrator at food when only one feeding site is present, they adjust their path integrator to a central location between sites when experiencing food at two or more locations. Together, this work provides a simple experimental paradigm and theoretical framework to advance investigations of the neural basis of path integration.

Olfactory navigation provides a tractable model for studying the circuit basis of sensori-motor transformations and goal-directed behaviour. Macroscopic organisms typically navigate in odor plumes that provide a noisy and uncertain signal about the location of an odor source. Work in many species has suggested that animals accomplish this task by combining temporal processing of dynamic odor information with an estimate of wind direction. Our lab has been using adult walking Drosophila to understand both the computational algorithms and the neural circuits that support navigation in a plume of attractive food odor. We developed a high-throughput paradigm to study behavioural responses to temporally-controlled odor and wind stimuli. Using this paradigm we found that flies respond to a food odor (apple cider vinegar) with two behaviours: during the odor they run upwind, while after odor loss they perform a local search. A simple computational model based one these two responses is sufficient to replicate many aspects of fly behaviour in a natural turbulent plume. In on-going work, we are seeking to identify the neural circuits and biophysical mechanisms that perform the computations delineated by our model. Using electrophysiology, we have identified mechanosensory neurons that compute wind direction from movements of the two antennae and central mechanosensory neurons that encode wind direction are are involved in generating a stable downwind orientation. Using optogenetic activation, we have traced olfactory circuits capable of evoking upwind orientation and offset search from the periphery, through the mushroom body and lateral horn, to the central complex. Finally, we have used optogenetic activation, in combination with molecular manipulation of specific synapses, to localize temporal computations performed on the odor signal to olfactory transduction and transmission at specific synapses. Our work illustrates how the tools available in fruit fly can be applied to dissect the mechanisms underlying a complex goal-directed behaviour.