Olfactory Mechanisms Supporting Attraction to e-Cigarette Odors

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PROJECT SUMMARY Sensory information from the environment guides behavior. In particular, odors are integral to finding food, identifying danger, and orchestrating social behaviors. Furthermore, odors can become salient cues when paired with reinforcers which may subsequently trigger cravings (e.g., compulsive eating, drug seeking, etc). Adolescent use of nicotine containing electronic cigarettes (e-cigarettes) has skyrocketed in recent years. Along with nicotine, e-cigarettes often contain appealing additives, such as fruit smells, which based upon their hedonics promote the acquisition and maintenance of e-cigarette/nicotine use in humans and rodents. Therefore, the odors emitted from e-cigarettes are of particular importance to their sensory perception. However, the brain systems responsible for mediating attraction to e-cigarette odors are unknown. The tubular striatum (TuS, also known as the olfactory tubercle) is an olfactory region that also receives modulatory input from midbrain dopaminergic (DA) neurons to inform decision-making. The TuS' distinct connectivity and dual roles in reward and sensory processing uniquely position it to mediate attraction to e-cigarette odors. The proposed F31 NRSA will use respiratory monitoring, behavior, site-specific pharmacology, optogenetics, and in vivo electrophysiology to test the hypothesis that dopaminergic systems of the TuS mediate attraction to e-cigarette odors in adolescent mice of both sexes. In Aim 1, I will test the hypothesis that DA's actions in the TuS are responsible for e-cigarette odor attraction. In Aim 2, I will test the hypothesis that TuS neurons expressing DA 1 receptors represent e- cigarette odors, and that their respiratory-coupled activity encodes the difference between e-cigarette odors containing strawberry additive (attractive) versus those without (unattractive). This project will reveal olfactory contributions to e-cigarette use and further, will uncover fundamental insights into brain systems involved in mediating odor attraction.