Structural mechanisms of odor recognition
How do olfactory receptors detect and discriminate the vast chemical world?
Odor detection poses a unique sensory challenge due the inordinate complexity of the chemical world. Natural aromas, from coffee to vinegar, are comprised of hundreds of distinct volatiles varying in molecular structure and physicochemical properties. To contend with this challenge, diverse species have converged on a common strategy in which odor identity is encoded through the combinatorial activation of large families of olfactory receptors (ORs), thus allowing a finite number of receptors to detect an almost infinite chemical world. To gain insight into the molecular basis for odorant recognition, we used cryo-EM to determinethe first structure of an insect olfactory receptor elucidating their basic architecture and revealed insight into the structural basis for promiscuous odor detection. Ongoing work aims to reveal the broader principles of how odors are recognized, by determining the structures of receptors tuned to different parts of chemical space and with diverse tuning properties. The goal of this work will be to shed ligh one the structural basis of chemical recognition in this family, laying the foundation for the rational design of novel classes of insect repellents and the development of electronic 'noses' for detection of environmental chemicals.
Mechanisms of Behavioral Evolution
How does evolution shape neural circuitry to generate novel behavioral traits?
Evolution has been tinkering with nervous systems for millions of years, ultimately giving rise to the incredible diversity of behaviors apparent across the animal kingdom. Yet, the basic principles that govern behavioral evolution remain largely unknown. The Ruta lab has been using the elaborate male courtship rituals of Drosophila as a window into the neural mechanisms of behavioral evolution. Courtship behaviors are amongst the most sophisticated and robust Drosophila display, offering a powerful system to delineate the biophysical, cellular, and circuit mechanisms of complex behavior. In past and ongoing work in D. melanogaster, we developed methods to record neural dynamics in courting males and revealed how multisensory signals govern mate recognition and how internal arousal states shape his ongoing performance. While we have made advances in elucidating the basic logic of these circuits, D. melanogaster represents a snapshot of just one evolutionary outcome. Across the Drosophila genus, courtship behaviors have rapidly diversified at almost every level, offering a unique opportunity to elucidate how the core neural algorithms of complex behavior have been tailored to species-specific needs. We have therefore been translating the rich neurogenetic toolkit from D. melanogaster to several of its close relatives, allowing us to systematically compare the homologous courtship circuits across a lineage and pinpoint sites of evolutionary adaptation. Using this comparative framework, we have been exploring how a male’s sexual arousal is encoded by a conserved circuit node, and how this core computation has been shaped through evolutionary selection to generate divergent mate preferences and motor displays. By studying neural circuits through the lens of evolution, we aim to provide distinct insights into their function and organization, allowing us to tease apart which neural motifs are conserved and constrained and which can vary and fuel behavioral diversity.
Mechanisms of Learning and Adaptive Behavior
How do individuals adapt to an ever-changing and dynamic world?
We use the concise architecture of olfactory circuits in Drosophila to explore the synaptic and circuit mechanisms that underlie rapid behavioral adaptations, allowing every individual within a species to appropriately respond to their unique and changing experience of the world. In recent work, we developed novel methods to record neural activity as flies navigate within a virtual olfactory environment, allowing us to begin to link neural and behavioral plasticity as animals explore and learn the causal relationships between sensory cues, actions, and outcomes. We revealed that the neuromodulator dopamine acts with unexpected spatial and temporal precision to rapidly reconfigure circuit properties, such that the same olfactory signal can be rerouted to distinct behavioral output pathways to underlie behavioral flexibility. Moreover, we showed that dopaminergic neurons carry multiplexed representations of both rewards and goal-directed actions, revealing how the same neuromodulatory systems that instruct learning shape ongoing behavior on a moment-to-moment timescale.