Behavioral and Neural Substrates of Odor-Guided Navigation in the Human Brain

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ABSTRACT Sensory systems have evolved to help meet the behavioral needs of organisms to ensure survival. Across the animal kingdom, two sensory functions are paramount: first, to identify specific objects in the environment and endow them with salience; and second, to move closer to objects of desire and away from objects that are best avoided. These properties – identification and localization – are the “what” and “where” questions of sensory information processing, respectively, and each of the senses provides a unique snapshot of the world that complements the other senses. In the unique case of olfaction, orthonasal and retronasal olfactory channels ensure that odor sources can be identified and tracked with fidelity at distal, proximate, and intraoral distances. This proposed project will focus on the “where” question of information processing in the human olfactory system. In particular, we aim to understand the capacities, constraints, and mechanisms by which odor cues orient and steer a navigator in the right direction. In this regard, a singular aspect of odors is their ability to travel through the air over long distances, such that the olfactory system can gather valuable predictive information not only about the physical location of an odorous source, but also about the navigator’s position within a physical landscape. Critically, while elegant neurobiological studies on odor navigation have been conducted in insects and birds, basic research on this topic in mammals, including humans, is sparse. Our planned studies are inspired by groundbreaking experiments showing that different types of neurons can encode and map physical spaces, including “place cells” (representing specific locations in space) and “grid cells” (representing an internal coordinate system to self-orient in this space). Here we will use functional magnetic resonance imaging (fMRI), virtual reality (VR) techniques, and computational methods to determine whether we can infer the presence of “grid-like” fMRI responses when human subjects navigate through an odor-rich two-dimensional landscape. In Aim 1, subjects will be asked to navigate a VR arena in which the only informative sensory cues are olfactory, enabling us to test whether subjects can learn the spatial relational positions among a set of odors, and whether grid-like responses arise during odor navigation. Aim 2 will test the stability of olfactory grid-like responses by assessing whether contextual changes in the VR arena induce remapping of olfactory cognitive maps. Aim 3 will test the behavioral limits of human olfactory navigation by progressively peeling away all remaining visual cues in the arena. Together these studies should bring fundamental understanding to the capacities and constraints of human olfactory navigation, and should highlight neural mechanisms underlying the “where” question of human olfaction, and more broadly, how the olfactory system tracks and locates odor sources in odiferous environments.