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

 描述（申请人提供）：冲动行为的特点是没有事先考虑就采取行动，缺乏克制反应的能力。紊乱的冲动性是许多精神疾病的主要特征，包括注意缺陷多动障碍（ADHD），行为障碍和反社会人格障碍，以及双相情感障碍中的暴食和躁狂发作。冲动行为的药物治疗是不够的，新的药物治疗方法的发展的限制因素是缺乏对冲动背后的神经回路的理解。在拟议的研究中，我的目标是通过使用新的转基因和体内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，成年人的5-羟色胺1B受体（5-HT 1BR）的非肾上腺素能细胞的表达影响冲动行为（反应抑制）冲动的组成部分。在这个项目中的实验的目的是表征的范围内的5-HT 1BR调制的多个子组成部分的冲动，包括冲动的选择（延迟满足）。此外，我将确定人口（5-HT 1BR的），有助于冲动行为和定义的神经回路机制。最后，通过使用最先进的体内钙成像方法，将测量在冲动行为期间5-HT 1BR对神经回路节点的影响。这些研究将作为转化项目的基础，研究冲动性障碍的神经基础，旨在确定开发冲动性是关键组成部分的精神疾病新疗法的目标。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，使我能够过渡到一个独立的主要研究者。

 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.