Mapping Thalamo-striatal Neuronal Circuits Underlying Motivational Drive

绘制动机驱动下的丘脑纹状体神经元回路

• 批准号: 10818040
• 负责人: Sofia Beas
• 金额: $ 7.39万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-03 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10818040
• 关键词: Address; Animals; Area; Behavior; Brain; Brain Stem; Data; Drug abuse; Electrophysiology (science); Ensure; Genetic Identity; Glutamates; Goals; Hypothalamic structure; Individual; Link; Major Depressive Disorder; Maps; Mediating; Mental Health; Mental disorders; Mission; Motivation; National Institute of Mental Health; Neurons; Obsessive-Compulsive Disorder; Pathway interactions; Play; Process; Quality of life; Research; Role; Signal Transduction; Structure of paraventricular nucleus of thalamus; insight; interdisciplinary approach; motivated behavior; mouse genetics; neuroimaging; neuromechanism; neuronal circuitry; novel; novel strategies; response; therapeutic target

Project Summary Motivated goal-directed behaviors act as mechanisms that ensure and promote survival in animals. However, the mechanisms that underlie motivated behaviors are not fully understood. This is important because deficits in motivation have been linked to various psychiatric disorders. Current research on this topic have largely focused on investigating the contribution of the dopaminergic meso-accumbens pathway to this process. However, the role that glutamatergic inputs to the NAc play in the control of motivation is far less clear. My previous research has shown that the paraventricular nucleus of the thalamus (PVT) sends prominent glutamatergic projections to the accumbens and in turn receives homeostatic signals from areas such as the hypothalamus and brainstem. As such, the PVT has been proposed as a brain area that integrates visceroceptive signals and to promote adaptive responses via projections to the NAc. Moreover, previous research and my preliminary data show that the PVT has two major distinct subpopulations of neurons, Type1PVT and Type2PVT, which differ on their genetic identity, connectional features, and functionality. However, the precise mechanisms by which these PVT projections to the NAc influences different components of motivated behavior remains unknown. To address this gap, we are examining the functional organization of the PVT-NAc neuronal circuit by using a multidisciplinary approach that includes mouse genetics, electrophysiology, neuroimaging and behavior. These findings will advance our understanding of the contributions of thalamo-striatal circuits promoting motivational drive that can create fundamental insights to develop novel approaches for individuals suffering from motivational deficits Relevance: Motivational deficits are a core feature of highly prevalent psychiatric disorders (e.g., drug- abuse or obsessive-compulsive disorder, major depressive disorder, and others), this research may provide insights into potential therapeutic targets for these psychiatric disorders. Lastly the research conducted here seeks to provide fundamental insight into the neural mechanisms that mediate motivated behaviors.

项目摘要 动机目标导向的行为作为确保和促进动物生存的机制。 然而，动机行为背后的机制还没有完全被理解。这一点很重要，因为 动力不足被认为与各种精神疾病有关。目前对这一主题的研究在很大程度上 重点研究了多巴胺能系膜伏隔通路在这一过程中的作用。 然而，谷氨酸能传入NAC在动机控制中所起的作用还远不清楚。我的 以往的研究表明，丘脑室旁核(PVT)发出的 谷氨酸能投射到伏隔核，进而接收来自 下丘脑和脑干。因此，PVT被认为是一个整合内脏感觉的大脑区域。 并通过对新AC的预测来促进适应性反应。此外，之前的研究和我的 初步数据显示，PVT有两个主要的不同神经元亚群，类型1PVT和类型2PVT， 它们在遗传身份、连接特征和功能上存在差异。然而，精确的机制 通过这些PVT向NAC的投射影响动机行为的不同成分 未知。为了解决这一差距，我们正在研究PVT-NAC神经元回路的功能组织 使用包括老鼠遗传学、电生理学、神经成像和行为学在内的多学科方法。 这些发现将促进我们对丘脑-纹状体回路促进 激励动力，可以创造基本的洞察力，为个人痛苦制定新的方法 从动机缺陷中 相关性：动机缺陷是高度流行的精神障碍的核心特征(例如，药物- 虐待或强迫症、严重抑郁障碍等)，这项研究可能会提供 对这些精神疾病的潜在治疗目标的洞察。最后，在这里进行的研究 旨在提供对调节动机行为的神经机制的基本见解。