Project Summary This project will investigate the neural computations underlying multisensory integration in the context of olfactory navigation. Olfactory navigation drives animal behaviors ranging from those critical for mankind’s survival, such as crop pollination, to those that are fantastically destructive, such as the location of human hosts by vectors of disease. Olfactory navigation is also an ideal paradigm for understanding how neural systems convert complex sensory stimuli into sequences of actions comprising a goal-directed task. To navigate odor plumes, animals must integrate potentially conflicting information streams from multiple sensory inputs, such as mechanosensory information from wind motion, as well as the timing and location of odor signals. I will focus on an information stream not yet investigated in olfaction: the direction of motion of traveling odor filaments. The direction of odor motion may contain information about the location of the odor source, which can reinforce information from local wind cues. This project will combine sophisticated behavioral paradigms, genetic silencing, calcium imaging, and theoretical modeling in a model system, the fruit fly Drosophila melanogaster, to characterize how odor motion is detected and used in natural plume navigation. Targeted neural manipulations are enabled by the wealth of genetic tools available in Drosophila system – in particular the recent identification of neuron types in (and development of genetic drivers for) higher-order olfactory processing centers. In the mentored (K99) portion of this grant, I will use behavioral recordings and optogenetic stimulation to characterize odor direction sensing in fruit flies, and how it integrates with wind sensing. In the latter portion of the K99, carrying over into the initial phase of the R00, I will use targeted genetic manipulations and calcium imaging to identify the neurons and brain regions involved in odor direction sensing, and to characterize how odor direction is encoded in the activity patterns of 2nd- and 3rd-order olfactory circuit neurons. This portion of the project is uniquely possible in the Drosophila system, whose well-mapped connectome allows causal perturbations of the information flow through the olfactory circuit hierarchy. In the latter portion of the R00, I will combine theoretical models with behavioral recordings to quantify how information from odor direction sensing can be optimally exploited in navigating naturalistic odor plumes. The proposal offers training in recording neural activity, as well as mentorship in the design of navigation assays and higher-order olfactory processing. Training will be provided by a strong mentorship and advising committee, consisting of co-mentors Thierry Emonet and Damon Clark, who offer complementary expertise in Drosophila olfactory navigation and in direction sensing in the Drosophila visual pathway, as well as advisors Justus Verhagen (virtual reality assay for o...