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

剖析血清素能和多巴胺能对冲动行为背后的神经回路的贡献。

基本信息

批准号：
9690972
负责人：
Katherine M Nautiyal
金额：
$ 24.9万
依托单位：
DARTMOUTH COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2021-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9690972
关键词：
Adult Advanced Development Aggressive behavior Antisocial Personality Disorder Attention deficit hyperactivity disorder Basic Science Behavior Behavioral Paradigm Binge Eating Binge eating disorder Bipolar Disorder Calcium Cells Chronic Clinical Research Cognitive Complex Conduct Disorder Data Development Dimensions Disease Disinhibition Dopamine Dopamine Agonists Dopamine D1 Receptor Dopamine D2 Receptor Foundations Genetic Polymorphism Head Health Human Image Imaging Device Imaging Techniques Imaging technology Impulsive Behavior Impulsivity Knock-out Knockout Mice Knowledge Learning Link Manic Maps Measures Mental disorders Mentorship Methods Microscope Motor Mus Neurons Nucleus Accumbens Pathogenesis Pharmacological Treatment Phenotype Play Population Psychiatric therapeutic procedure Regulation Research Research Personnel Research Training Rodent Serotonin Serotonin Receptor 5-HT1B Signal Transduction Societies Techniques Time Tissues Training Transgenic Mice Transgenic Organisms Ventral Tegmental Area Viral Work addiction career design experimental study gamma-Aminobutyric Acid genetic technology imaging modality improved in vivo calcium imaging in vivo imaging knock-down mouse model neural circuit neural correlate novel public health relevance receptor relating to nervous system response skills trait impulsivity

项目摘要

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.

描述（由适用提供）：冲动行为的特征是无预见的行为，并且缺乏扣留反应的能力。无序的冲动行为是许多精神疾病的主要特征，包括注意力缺陷多动障碍（ADHD），行为障碍和反社会人格障碍，以及双相情感障碍中的暴饮暴食和躁狂发作。冲动行为的药理治疗不足，而新的药理学治疗的发展是对冲动性潜在的神经元回路的理解。在拟议的研究中，我旨在通过使用新型的转基因和体内成像工具来研究该领域的进展，以研究冲动性的神经元电路。我以前的工作表明，血清素1b受体（5-HT1BR）在非杂色细胞上的成年表达会影响冲动的作用（反应抑制）该项目中的实验旨在表征5-HT1BR调制的范围，以表征脉冲选择的多个脉冲子组成部分的范围，包括冲动选择（包括脉动的满足）。另外，我将确定人口（5-HT1BR的s，有助于冲动行为并定义神经回路机制。最后，通过使用最先进的体内钙像成像方法，5-HT1BR的影响，5-HT1BR对神经行为的节点的效果将在脉冲行为中进行调查。在冲动过程中，将作为基化的依据来衡量。为了确定对冲动性的精神疾病的新疗法的发展，这是一个关键的组成部分，该项目将为我提供职业心态以及技术，统计和理论培训，以使我能够过渡到独立的主要研究员。