Olfactory Mechanisms Supporting Attraction to e-Cigarette Odors

项目总结 来自环境的感官信息指导行为。特别是，气味是寻找食物不可或缺的一部分， 识别危险，并协调社会行为。此外，当气味配对时，气味可以成为显著的线索 使用增强剂，随后可能会引发渴望(例如，强迫性进食、寻求毒品等)。青少年 近年来，含有尼古丁的电子烟(电子烟)的使用量激增。与.一起 尼古丁，电子烟通常含有诱人的添加剂，如水果气味，这是基于它们的快乐性。 促进电子烟/尼古丁在人类和啮齿动物中的使用和维持。因此， 电子烟散发出的气味对他们的感官感知特别重要。然而，大脑 负责调节电子烟气味吸引力的系统尚不清楚。管状纹状体(TU，又称纹状体 嗅结节)是一个嗅觉区域，也接受来自中脑的调制输入 多巴胺能(DA)神经元为决策提供信息。TU在奖励中的独特连接性和双重角色 感官处理独特地定位了它，以调节对电子烟气味的吸引。建议的F31 NRSA 将使用呼吸监测、行为、特定部位的药理学、光遗传学和活体电生理学 为了验证青少年对电子烟气味的吸引作用，TU的多巴胺能系统起中介作用的假设 不同性别的小鼠。在目标1中，我将测试DA在TU中的行为应对电子烟负责的假设 气味吸引。在目标2中，我将检验这样一种假设，即表达DA1受体的TUS神经元代表e- 香烟气味，以及它们的呼吸耦合活动编码了电子烟气味之间的差异 含有草莓添加剂的(吸引人的)与不含草莓添加剂的(不吸引人的)。这个项目将揭示嗅觉 对电子烟使用的贡献，并进一步揭示对参与电子烟使用的大脑系统的基本见解 调节气味吸引。

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.