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: 10892005
• 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/10892005
• 关键词: Address; Automobile Driving; Autopsy; Behavior; Behavioral; Brain region; Cells; Classification; Complex; Corpus striatum structure; Data; Disease; Disinhibition; Dopamine; Dopamine D1 Receptor; Dopamine D2 Receptor; Eating; Energy Intake; Feeding behaviors; Food Intake Regulation; Genetic Techniques; Globus Pallidus; Glutamates; Hypothalamic structure; LH Cell; Lateral; Lesion; Link; Literature; Maps; Mediating; Methods; Motivation; Neurons; Nucleus Accumbens; Obesity; Pathway interactions; Phenotype; Population; Positioning Attribute; Research; Rewards; Role; Synapses; Techniques; Testing; Tissues; Training; Transgenic Mice; Ventral Striatum; Viral; behavioral study; brain pathway; career; cell type; designer receptors exclusively activated by designer drugs; energy balance; experience; feeding; food consumption; gamma-Aminobutyric Acid; genetic approach; hedonic; hypocretin; melanin-concentrating hormone; nerve supply; neuronal circuitry; pharmacologic

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 and chemogenetic approaches I will determine the cell-types implicated in each component of this three-part circuitry, and how they mediate feeding behaviors. I hypothesize that GABAergic striatal projection neurons expressing the dopamine D2 receptor in the NAcS preferentially innervate GABAergic cells in the VP, which in turn disinhibit 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.

食物消耗是物种生存和理解神经回路的基础