Habenular regulation of nicotine intake
Dr. Paul J. Kenny; Neuroscience Drug Discovery Instistute
October 6 in the Fralin Auditorium, Fralin Hall 102
Hosted by Dr. G Hodes
Rates of relapse are remarkably high in tobacco smokers attempting to quit the habit, particularly during the earliest stages of withdrawal when nicotine craving peaks, yet underlying mechanisms of nicotine craving and relapse remain poorly understood. The septum plays key roles in anxiety, irritability, memory and reward, processes negatively impacted by withdrawal in smokers, but septal involvement in nicotine craving and relapse has not been investigated. I will present evidence suggesting that the triangular nucleus of the septum (TNS) provides a major source of excitatory input to neurons in the medial habenula, a brain region that controls the motivational properties of nicotine. We find that TNS neurons oscillate at theta frequency, with this pattern of firing optimally enhancing TNS-derived excitatory signaling in the habenula. Furthermore, we find that nicotine withdrawal induces profound deficits in septal-derived excitatory but not inhibitory transmission in habenula. Nicotine withdrawal triggers craving-like responses for the drug only when rats consume quantities of nicotine sufficient to disrupt TNS-derived excitatory transmission in habenula. Selective lesion or chemogenetic inhibition of the TNSàhabenula circuit is shown to enhance withdrawal-induced nicotine seeking whereas stimulation of this circuit attenuates this craving response. These findings suggest that perturbation of septal communication with the habenula plays a critical role in nicotine craving and relapse.