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： 餐点的大小经过仔细的规则，以防止过度喂食。 由脑干区域（例如孤立区的尾核（CNT））归因于直接接收的 相反，胃肠道的短期感觉反馈。 下丘脑电路和瘦素 通过调节脑干中的TheShess Short-Taterm信号的终止 在这些长期和短期系统之间对OFOD的控制是批判性的，但是它是如何的 在基础脑干电路的动力学中编码仍然未知。 在这些细胞类型中涉及的食物摄入量的类型。 胰高血糖素（GCG）神经元在我最近的研究中尤为重要。 这两种细胞类型的首次神经记录在醒着的行为小鼠中。 在餐食开始时，通过味道（例如味道）迅速激活 概念上的进步为我创造了一个机会，以调查一个长期以来的信号的问题 长期能量平衡模块化脑干电路以控制饮食终止。 通过调查两个长期能量平衡与阿古蒂相关肽（AGRP）的常客如何 神经元和瘦素 - 模块化PRLH或GCG神经元动力学或它们对喂养行为的控制 这些结果将揭示长期系统模块化脑干电路如何适用于常规膳食大小，这是 总体食物摄入的重要决定因素，在敬拜等条件下可能会失调。