Olfactory Mechanisms Supporting Attraction to e-Cigarette Odors

项目摘要 来自环境的感官信息引导行为。特别是气味是寻找食物不可或缺的 识别危险，协调社会行为。此外，气味可以成为显着的线索时，配对 使用可能随后引发渴望的食物（例如，强迫性饮食、吸毒等）。青少年 近年来，含有尼古丁的电子香烟（e-cigarettes）的使用激增。沿着 尼古丁，电子烟往往含有吸引人的添加剂，如水果气味，这是基于他们的快感 促进人类和啮齿动物获得和维持电子烟/尼古丁的使用。因此 从电子香烟发出的气味对于他们的感官知觉特别重要。然而，大脑 负责介导对电子烟气味的吸引的系统是未知的。管状纹状体（TuS，也 称为嗅结节）是一个嗅觉区域，也接受来自中脑的调节输入 多巴胺能（DA）神经元来告知决策。TuS独特的连接性和奖励的双重角色 和感官处理独特地将其定位为介导对电子烟气味的吸引。F31 NRSA 将使用呼吸监测、行为、特定部位药理学、光遗传学和体内电生理学 为了验证TuS的多巴胺能系统介导青少年对电子烟气味的吸引力的假设， 两种性别的老鼠。在目标1中，我将测试DA在Tu S中的行为对电子烟负责的假设 气味吸引力在目的2中，我将检验表达DA 1受体的TuS神经元代表e- 香烟气味，并且它们的相互作用耦合的活动编码了电子烟气味之间的差异 含有草莓添加剂（有吸引力的）与不含草莓添加剂（没有吸引力的）。这个项目将揭示嗅觉 对电子烟使用的贡献，并进一步揭示了大脑系统的基本见解， 介导气味吸引。

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.