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“Inverse translational” mouse models of human olfactory coding and perception

Neuroimaging studies of the human olfactory system have provided many insights into the links between brain anatomy, brain functional activity, and behavioral and perceptual states. However, apart from a small handful of experiments, most of these imaging studies are fundamentally correlative, meaning that attempts to establish whether a given brain region or network of brain regions is either necessary or sufficient to support odor perception remains speculative. In new experiments underway at U Penn, we are adapting fMRI paradigms from our human work and translating these to mice. The main goal is to determine whether the brain areas identified in our human studies are causally related to odor-guided behavior and perception. The strategy is to train awake behaving mice to perform an olfactory perceptual learning task while head-fixed within a high-field (9.4-Tesla) MR scanner, and then to incorporate different experimental manipulations, using optogenetic, surgical, and pharmacological approaches, as a way of establishing a mechanistic role for select neuronal cell types, pathways, and neurotransmitter systems in the expression of different olfactory perceptual and cognitive states.