Mapping the neuronal circuitry underlying indirect striatal to hypothalamic connectivity and its role in feeding

绘制间接纹状体与下丘脑连接的神经元回路及其在进食中的作用

• 批准号: 10670581
• 负责人: Miriam E. Bocarsly
• 金额: $ 5.81万
• 依托单位: RUTGERS BIOMEDICAL AND HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10670581
• 关键词: Attention; Behavior; Brain region; Cells; Complex; Corpus striatum structure; Disease; Disinhibition; Dopamine D2 Receptor; Eating; Energy Intake; Feeding behaviors; Fiber; Food Intake Regulation; Globus Pallidus; Hypothalamic structure; Lateral; Link; Maps; Mediating; Methods; Motivation; Neurons; Nucleus Accumbens; Obesity; Pathway interactions; Periodicity; Photometry; Population; Research; Rewards; Role; Scanning; Techniques; Training; Ventral Striatum; Viral; behavioral study; brain pathway; cell type; feeding; food consumption; gamma-Aminobutyric Acid; genetic approach; hedonic; in vivo; neuronal circuitry

The Project Summary Food consumption is fundamental to species survival and understanding the neuronal circuitry underlying feeding behaviors is of the utmost importance. Amassing evidence supports the idea that control of caloric intake is complex and involves calculations of hedonic value, reward and motivation. Thus, it requires interactions between brain regions classically implemented in feeding (such as the lateral hypothalamus; LH) and the regions modulating reward (such as the ventral striatum). While the intersection of these regions has been suggested, the cell-type specific circuitry linking these pathways is poorly understood. The objective of this proposal is to further elucidate the cell-type specific circuitry underlying striatal-to-lateral hypothalamic connections and determine its role in feeding, while gaining training in new neuronal circuitry mapping techniques. There is evidence that the striatum exerts its control over feeding behaviors by interfacing with the LH. Previous research indicates that the ventral striatum, and specifically the nucleus accumbens shell (NAcS), and the LH are connected via a direct pathway. However, rudimentary tracing and behavioral studies have suggested a second, indirect pathway, with the NAcS projecting to the ventral pallidum (VP), which in turn projects to the LH. However, despite this initial evidence, cell-type specific, neuronal circuitry in this indirect pathway remains unknown. Using viral tracing methods, in vivo fiber photometry, fast-scan cyclic voltammetry and chemogenetic approaches I will determine the cell-types implicated in each component of this three-part circuitry, and how they mediate feeding behaviors. While I have growing evidence that GABAergic striatal projection neurons expressing the dopamine D2 receptor in the NAcS preferentially innervate the VP to control feeding, I will now turn my attention to the second part of the circuitry. I hypothesize that this population of GABAergic cells in the VP, which receives NAcS input, in turn disinhibits LH GABA neurons to facilitate feeding. Furthermore, in understanding the brain pathways and connectivity underlying food intake behaviors, this project will ultimately allow us to better understand perturbations that occur in disease states such as obesity.

项目总结 食物摄取是物种生存和了解其背后的神经回路的基础 摄食行为是最重要的。越来越多的证据支持这样一种观点：控制卡路里摄入量 是复杂的，涉及享乐价值、奖励和动机的计算。因此，它需要交互 在经典的摄食时执行的大脑区域(如下丘脑外侧区；LH区)和 调节奖赏(如腹侧纹状体)。虽然这些区域的交叉点已经被提出， 连接这些通路的细胞类型的特定电路还知之甚少。这项建议的目的是 进一步阐明纹状体到下丘脑外侧连接的细胞类型特异性回路和 确定它在进食中的作用，同时接受新的神经回路映射技术的培训。 有证据表明，纹状体通过与黄体生成素的相互作用来控制取食行为。 先前的研究表明，腹侧纹状体，特别是伏隔核壳(NaCs)，以及 左翼通过一条直接通道相连。然而，初步的追踪和行为研究表明 第二种是间接通路，NAC投射到腹侧苍白球(VP)，后者又投射到 左撇子。然而，尽管有这一初步证据，这种间接途径中的特定细胞类型的神经元回路仍然存在。 未知。利用病毒示踪、体内纤维光度法、快速扫描循环伏安法和化学发生法 方法I将确定此三部分电路的每个组件所涉及的单元类型，以及它们如何 调节进食行为。虽然我有越来越多的证据表明GABA能纹状体投射神经元表达 NAC中的多巴胺D2受体优先支配VP来控制摄食，现在我将转向我的 注意电路的第二部分。我假设VP中的GABA能细胞群， 接受NACS输入，进而解除对LHGABA神经元的抑制，以便于进食。 此外，在理解大脑通路和食物摄入行为背后的连接时，这一点 该项目最终将使我们能够更好地了解肥胖等疾病状态下发生的扰动。