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

项目摘要 父R 00补助金的重点是冲动行为，其特点是没有事先考虑的行为 并且缺乏抑制旧反应的能力。紊乱的冲动是许多精神病患者的主要特征， 包括注意力缺陷多动障碍（ADHD）、行为障碍和反社会人格在内的疾病 以及双相情感障碍中的暴饮暴食和躁狂发作。药物治疗 冲动行为是不够的，并在新的药物治疗的发展的限制因素 缺乏对冲动背后的神经回路的理解在以前的工作中，我们确定了一个角色， 5-羟色胺1B（5-HT 1B）受体在冲动调节中的作用，父母R 00补助金中的研究是 重点是了解电路级机制，通过它发生。一组研究用于 体内钙成像以评估5-HT 1B对冲动行为的细胞相关性的影响。这 行政补充建议建立动态和预测贝叶斯模型的细胞编码 为了更好地了解神经活动如何影响神经系统， 模式助长了冲动。具体来说，我们将讨论神经编码如何在几天内保持稳定， 它在病理性冲动的状态下发生变化，以及它如何在多个主体之间共享。总体而言，这 该项目将有助于更好地了解无序冲动的神经基础，并告知目标 用于开发新的治疗精神疾病的方法，其中冲动是一个关键组成部分。

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.