Nicotine addiction in the form of habitual tobacco use is the leading cause of premature death in the United States and costs at least $170 billion in healthcare-related expenses each year. In addition to its addictive qualities, nicotine triggers a plethora of respiratory, cardiovascular, gastrointestinal, and immune disorders, reflecting its actions in the brain and also in the body of smokers. While it is well established that the addictive properties of nicotine are related to its direct pharmacological actions on nicotinic acetylcholine receptors (nAChRs) located in reward and motivation brain circuits, recent evidence suggests that noxious effects of nicotine mediated by brain aversion circuits plays a significant role. For example, our laboratory recently established that the nucleus of the solitary tract regulates noxious response to nicotine and controls drug intake. However, it is unclear if nicotine acts on the NTS directly through locally expressed nAChRs or if nicotine also recruits NTS activity indirectly the dense innervation by the nodose ganglia (NG), with its vagally-derived afferents that route sensory information from the periphery to the brain. Data from our laboratory and others suggests that the actions of nicotine in the periphery can activate aversion neurocircuitry, but the role for such sensory information in regulating the addiction-related actions of nicotine has not been explored. I am currently addressing these unknowns using a combination of rodent models of addiction, cell type-specific manipulations, and genome editing & sequencing methodologies.