Mapping Thalamo-striatal Neuronal Circuits Underlying Motivational Drive

项目摘要 有动机的目标导向行为是确保和促进动物生存的机制。 然而，动机行为的机制并没有完全理解。这很重要因为 缺乏动力与各种精神疾病有关。目前对这一问题的研究主要是 集中于研究多巴胺能meso-albens通路对该过程的贡献。 然而，对NAc的兴奋性输入在控制动机中所起的作用还远不清楚。我 先前的研究表明，丘脑室旁核（PVT）发出显著的 神经元投射到小脑，反过来又从诸如小脑的区域接收稳态信号， 下丘脑和脑干。因此，PVT被认为是整合内脏感受的脑区， 信号，并通过对NAc的预测来促进适应性反应。此外，以前的研究和我的 初步数据显示，PVT具有两个主要的不同神经元亚群，1型PVT和2型PVT， 它们在遗传特性、连接特征和功能上不同。然而，精确的机制 通过这些PVT投射到NAc影响动机行为的不同组成部分， 未知为了解决这一差距，我们正在通过以下方式检查PVT-NAc神经元回路的功能组织 使用多学科的方法，包括小鼠遗传学，电生理学，神经成像和行为。 这些发现将促进我们对丘脑-纹状体回路促进神经元再生的作用的理解。 动机驱动力，可以创造基本的见解，为遭受痛苦的个人开发新的方法 从动机缺陷 相关性：动机缺陷是高度流行的精神疾病的核心特征（例如，药物- 虐待或强迫症，严重抑郁症，和其他），这项研究可能会提供 这些精神疾病的潜在治疗靶点的见解。最后，在这里进行的研究 旨在提供基本的洞察神经机制，调解动机行为。

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.