Dissecting serotonergic and dopaminergic contributions to the neural circuits underlying impulsive behavior.



 DESCRIPTION (provided by applicant): Impulsive behavior is characterized as acting without forethought and lacking the ability to withold responses. Disordered impulsivity is a major feature of a number of psychiatric disorders including attention deficit hyperactivity disorder (ADHD), conduct disorder, and antisocial personality disorder, as well as binge eating and manic episodes in bipolar disorders. Pharmacological treatments for impulsive behavior are inadequate, and a limiting factor in the development of new pharmacological treatments is a lack of understanding of the neural circuits underlying impulsivity. In the proposed research, I aim to extend progress in this field by using novel transgenic and in vivo imaging tools to study the neural circuitry underlying impulsivity. My previous work shows that adult expression of the serotonin 1B receptor (5-HT1BR) on non-serotonergic cells influences the impulsive action (response inhibition) component of impulsivity. The experiments in this project aim to characterize the scope of 5-HT1BR modulation of the multiple subcomponents of impulsivity including impulsive choice (deferred gratification). Additionally, I will identify the population(s of 5-HT1BRs that contribute to impulsive behavior and define the neural circuit mechanisms. Lastly, through the use of state-of- the-art in vivo calcium imaging methods, the effect of 5-HT1BRs on nodes of the neural circuits will be measured during impulsive behaviors. These studies will serve as a foundation for translational projects investigating the neural basis of disordered impulsivity with the aim to identify targets for the development of new treatments for psychiatric disorders in which impulsivity is a key component. Additionally, this project will provide me with career mentorship as well as technical, statistical, and theoretical training to enable my transition to an independent primary investigator.