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

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Project Summary The parent R00 grant is focused on impulsive behavior which 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 previous work we identified a role for the serotonin 1B (5-HT1B) receptor in the modulation of impulsivity, and the research in the parent R00 grant is focused on understanding the circuit-level mechanisms through which this occurs. One set of studies used in vivo calcium imaging to assess the effect of 5-HT1B on cellular correlates of impulsive behavior. This administrative supplement proposes to build dynamic and predictive Bayesian models of the cellular encoding of impulsive behavior, using data collected in the R00, in order to better understand how neural activity patterns subserve impulsivity. Specifically we will address how the neural encoding is stable across days, how it changes in states of pathological impulsivity, and how it is shared across multiple subjects. Overall, this project will contribute to a better understanding of the neural basis of disordered impulsivity and inform targets for the development of new treatments for psychiatric disorders in which impulsivity is a key component.