Cracking the Olfactory Code

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Project Summary (Overall: Cracking the Olfactory Code) Sensation drives perception, which informs decisions and actions. Olfaction is the main sense used by most animals to interact with the environment. However, olfaction remains shrouded in mystery — we do not know which molecular odorant features matter to the olfactory system and which do not, how information about these features is recombined to create holistic odor representations within the brain, or how those representations relate to perception. As a consequence, we lack an empirical understanding of the core transformations taking place at each stage of olfactory processing, which ultimately lead to perception and behavior. In addition, we lack a clear theoretical framework for understanding how a stimulus space that is both discrete and high-dimensional yields a perceptual space that is continuous and low dimensional. Because the olfactory system is “shallow” — meaning that within two synapses information about complete odor objects is abstracted and generalized — understanding this specific circuit will also afford general insight both into architecturally-related allocortical brain regions critical to behavior (e.g., cerebellum, hippocampus), and into cortical centers that play a key role in integrating diverse sources of information (e.g., prefrontal cortex, posterior parietal cortex). Here we propose to reveal the computational logic of olfaction by collecting the first system-wide dataset of neural and perceptual responses to a large, principled set of odorants, and by applying a unified statistical and theoretical approach to its interpretation. This project will convene research groups with expertise that spans neurobiology, and will leverage recent technical advances in molecular genetics, neural imaging, electrophysiology, opto- and chemogenetics, human psychophysics, and machine learning to interrogate all levels (from peripheral receptors to cortex to perceptual and behavioral output) of the olfactory system. Taken together, these experiments will establish a reference dataset that reveals the key transformations performed by the olfactory system, test a key unifying theory for olfaction, and create a community-wide resource that will prompt new theory and experiment. This work will also have wide-ranging implications for our general understanding of how sensory information is organized in the brain to facilitate adaptive action.