Investigating how long-term signals modulate brainstem satiation circuits

研究长期信号如何调节脑干饱足回路

• 批准号: 10752497
• 负责人: Truong Ly
• 金额: $ 4.36万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10752497
• 关键词: Ablation; Address; Adult; Area; Automobile Driving; Behavior; Brain; Brain Stem; Cells; Cholecystokinin; Cranial Nerves; Cues; Eating; Elements; Exhibits; Fasting; Feedback; Feeding behaviors; Food; Gastrointestinal tract structure; Glucagon; Glutamates; Hormones; Hunger; Hypothalamic structure; Infusion procedures; Ingestion; Leptin; Logic; Measures; Mus; Neurons; Nucleus solitarius; Nutrient; Obesity; Oral Ingestion; Peptides; Phase; Photometry; Population; Prolactin-Releasing Hormone; Regulation; Reporting; Role; Satiation; Sensory; Signal Transduction; Starvation; Structure; Structure of nucleus infundibularis hypothalami; System; Taste Perception; Testing; Time; Work; awake; cell type; energy balance; experimental study; feeding; in vivo; in vivo evaluation; mature animal; neonatal mice; neonate; neural; optogenetics; prevent; response; sensory feedback

Project Abstract: The size of a meal is carefully regulated to prevent over- or under-feeding. Direct control of meal size is attributed by brainstem areas, such as the caudal nucleus of the solitary tract (cNTS), that directly receive short-term sensory feedback from the GI tract during feeding. In contrast, the indirect controls, which include hypothalamic circuits and leptin, are hypothesized to encode long-term energy balance and regulate meal termination by modulating the potency of these short-term signals sensed in the brainstem. Interactions between these long-term and short-term systems are critical for the control of food intake, but how it is encoded in the dynamics of the underlying brainstem circuits remains unknown. The cNTS contains many cell types that are involved in controlling food intake. Among these cell types, prolactin releasing hormone (PRLH) and glucagon (GCG) neurons are particularly important for meal termination. In my recent studies, I performed the first neural recordings of these two cell types in awake behaving mice. I found unexpectedly that these cells were rapidly activated at the start of a meal by feedforward signals such as taste. These technical and conceptual advances create an opportunity for me to investigate the longstanding question of how signals of long-term energy balance modulate brainstem circuits to control meal termination. I propose here to address this question by investigating how two regulators of long-term energy balance – Agouti-related peptide (AgRP) neurons and leptin – modulate PRLH or GCG neuron dynamics or their control of feeding behavior. Together these results will reveal how long-term systems modulate brainstem circuits to regulate meal size, which is an important determinant of overall food intake and can be dysregulated in conditions like obesity.

项目摘要： 每顿饭的大小都经过仔细的控制，以防止进食过多或过少。直接控制餐量是 由脑干区域，如孤束尾侧核(CNTS)直接接收 进食期间来自胃肠道的短期感觉反馈。相比之下，间接控制包括 下丘脑回路和瘦素被认为是编码长期能量平衡和调节膳食的物质。 通过调节脑干中感知到的这些短期信号的效力来终止。互动 这些长期和短期系统之间的关系对于控制食物摄入量至关重要，但它是如何 编码在基本脑干回路的动力学中的信息仍不清楚。碳纳米管含有大量的细胞 参与控制食物摄入量的类型。在这些细胞类型中，催乳素释放激素(PRLH) 而胰高血糖素(GCG)神经元对终止进餐尤为重要。在我最近的研究中，我表演了 这两种细胞类型在清醒行为小鼠中的第一次神经记录。我意外地发现这些细胞 在一顿饭开始时被味觉等前馈信号迅速激活。这些技术和 概念上的进步为我提供了一个机会来研究长期存在的问题，即信号是如何 长期的能量平衡调节脑干回路来控制食物的终止。我建议在这里谈一谈 这个问题是通过调查两个长期能量平衡的调节者--Agti相关肽(AgRP) 神经元和瘦素调节PRLH或GCG神经元动力学或它们对摄食行为的控制。同舟共济 这些结果将揭示长期系统如何调节脑干回路来调节食物的大小，这是一种 这是总食物摄入量的重要决定因素，在肥胖等情况下可能会受到失调。