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

 描述(由申请人提供)：冲动行为的特征是没有事先考虑就采取行动，缺乏抵抗旧反应的能力。冲动障碍是许多精神障碍的主要特征，包括注意力缺陷多动障碍(ADHD)、品行障碍和反社会人格障碍，以及双相情感障碍中的暴饮暴食和躁狂发作。对冲动行为的药物治疗是不够的，而开发新的药物治疗的一个限制因素是缺乏对冲动背后的神经回路的了解。在这项拟议的研究中，我的目标是通过使用新的转基因和活体成像工具来研究冲动背后的神经回路，从而扩大这一领域的进展。我以前的工作表明，成年后5-羟色胺1B受体(5-HT1BR)在非5-羟色胺能细胞上的表达会影响冲动的冲动行为(反应抑制)成分。本项目的实验旨在表征冲动的多个子成分，包括冲动选择(延迟满足)的5-HT1BR调制的范围。此外，我将确定导致冲动行为的人群(S)5-HT1BR，并定义神经回路机制。最后，通过使用最先进的活体钙成像方法，将测量脉冲行为中5-HT1BRs对神经回路节点的影响。这些研究将作为研究冲动障碍的神经基础的翻译项目的基础，目的是确定开发冲动是关键组成部分的精神障碍新疗法的目标。此外，这个项目将为我提供职业指导以及技术、统计和理论培训，使我能够过渡到独立的主要调查员。

 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.