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

项目摘要 家长R00奖助金的重点是冲动行为，其特征是采取行动时没有事先考虑 以及缺乏抵御老年反应的能力。冲动障碍是许多精神病患者的一个主要特征 障碍包括注意力缺陷多动障碍(ADHD)、品行障碍和反社会人格 躁郁症，以及暴饮暴食和躁狂发作的双相情感障碍。治疗的药物治疗 冲动行为是不充分的，是开发新的药物治疗的限制因素 是对冲动背后的神经回路缺乏了解。在之前的工作中，我们确定了 5-羟色胺1B(5-HT1B)受体在冲动的调节中的作用，以及在亲本R00资助中的研究 重点是了解发生这种情况的电路级机制。其中一组研究用于 活体钙成像以评估5-HT1B对冲动行为的细胞相关性的影响。这 行政副刊建议建立细胞编码的动态和预测性贝叶斯模型 使用在R00中收集的数据，以更好地理解神经活动是如何 模式抑制了冲动。具体地说，我们将解决神经编码如何在几天内保持稳定，如何 它改变了病理性冲动的状态，以及如何在多个受试者之间共享。总体而言，这 项目将有助于更好地理解无序冲动的神经基础，并向目标提供信息 用于开发冲动是关键因素的精神障碍的新疗法。

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.