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

• 批准号: 9903618
• 负责人: Katherine M Nautiyal
• 金额: $ 9.32万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9903618
• 关键词: Address; Administrative Supplement; Antisocial Personality Disorder; Attention deficit hyperactivity disorder; Bayesian Modeling; Behavior; Behavioral; Binge Eating; Bipolar Disorder; Brain; Calcium; Cell model; Cells; Classification; Computer Simulation; Conduct Disorder; Data; Data Collection; Development; Disease; Dopamine; Exhibits; Financial Hardship; Funding; Generations; Goals; Grant; Health; Imaging technology; Impairment; Impulsive Behavior; Impulsivity; Individual; Manic; Measures; Mental disorders; Microscope; Mus; Neurons; Parents; Pathologic; Pattern; Pharmacological Treatment; Phenotype; Population Analysis; Psychiatric therapeutic procedure; Research; Role; Serotonin; Serotonin Receptor 5-HT1B; Societies; Testing; Training; Work; addiction; base; behavior measurement; behavior test; computational neuroscience; computer framework; gamma-Aminobutyric Acid; genetic technology; in vivo calcium imaging; markov model; microendoscope; mouse model; network models; neural circuit; neural patterning; relating to nervous system; response

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.

项目摘要 父级R00赠款的重点是冲动行为，该行为被认为是行动而没有​​预见的 并且缺乏脱颖而出的反应的能力。突变性无序是许多精神病学的主要特征 疾病包括注意力缺陷多动障碍（ADHD），行为障碍和反社会人格 疾病以及双相情感障碍中的暴饮暴食和躁狂发作。药理治疗 冲动行为不足，是新药理治疗发展的限制因素 是缺乏对冲动性神经回路的了解。在以前的工作中，我们确定了 在冲动性调节中，5-羟色胺1B（5-HT1B）受体，父级R00授予的研究为 专注于理解发生这种情况的电路级机制。一组用于 体内钙成像以评估5-HT1b对脉冲行为相关性的影响。这 行政补充提议建立动态和预测的蜂窝编码模型 使用R00中收集的数据的冲动行为，以更好地了解神经活动 模式予以冲动。具体而言，我们将解决神经编码在几天之间的稳定性，如何 它改变了病理冲动状态，以及如何在多个主题中共享。总体而言，这 项目将有助于更好地理解冲动性的神经基础，并告知目标 为了开发新的精神疾病疗法，冲动是关键组成部分。