CRCNS Research Proposal: Collaborative Research: Mechanisms and dynamics of retronasal olfactory coding

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How do our brain, nose, and mouth work together to generate the flavor of food and drink? When flavor perception goes wrong, can this play a role in diseases like obesity? The sense of smell is very important for perceiving flavor, largely because of odors that originate in the mouth and are exhaled through the nose via the back of the throat in a a process called retronasal olfaction. In this study, researchers from the University of Arkansas, the Virginia Commonwealth University, and Southeastern Methodist University are teamed up to gain better understanding of how retronasal olfaction works using rats as an animal model. The researchers combine direct measurements of the brain in action together with computer simulations of air flow through the nose and neural networks. They are testing the idea that different forces in the nose caused by reversing airflow through the nasal cavity are responsible for how the brain distinguishes exhaled retronasal odors from inhaled odors. In addition, the researchers offer training opportunities at each of the three institutions and are developing an educational video game aimed at introducing users to basic concepts of neurobiology and cognitive neuroscience. Smells that enter the nose retronasally, i.e., from the back of the nasal cavity, play an essential role in flavor perception, yet many questions about the neuroscience of retronasal olfaction remain unanswered. How does simply reversing the direction of air flow through the nasal cavity result in different neural input to the olfactory bulb (OB)? How are retronasal and orthonasal (inhaled) olfactory signals encoded at the level of spiking neurons in the OB? How do interactions within OB circuits facilitate selective response to retronasal versus orthonasal stimuli? In this study, researchers from the University of Arkansas, the Virginia Commonwealth University, and Southeastern Methodist University are teamed up to answer these questions, guided by a two-part hypothesis. First, they hypothesize that, at the sensory periphery, retro- and orthonasal stimuli produce distinct spatiotemporal patterns of mechanosensory excitation of olfactory receptor neurons. Second, they hypothesize that, in the OB, cell-type-specific inhibitory circuit interactions are crucial for dynamic changes in retronasal coding. To test these hypotheses, the research team is combining high-density multi-electrode recordings in rat OB with fluid dynamics computer simulations based on the three-dimensional shape of the nasal cavity of the same animals. Moreover, the team is performing state-of-the-art realistic computational modeling to identify OB circuit-level principles of retronasal coding. This work is expected to generate new understanding of the neural basis of retronasal olfaction that includes both peripheral mechanisms in the nose and central mechanisms at the level of M/T cells in the OB. This project is jointly funded by the cross-directorate Collaborative Research in Computational Neuroscience program, the Established Program to Stimulate Competitive Research(EPSCoR), and the MPS Office of Multidisciplinary Activities.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.