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： 仔细调节膳食量，以防止喂食过量或不足。 归因于脑干区域，例如孤束尾核（cNTS），直接接收 相比之下，喂养期间胃肠道的短期感觉反馈包括间接控制。 下丘脑回路和瘦素，竞相编码长期能量平衡和调节膳食 通过调节脑干中感知到的这些短期信号的效力来终止。 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，但它是如何实现的 cNTS 包含许多细胞，但其编码的底层脑干回路的动态仍然未知。 在这些细胞类型中，催乳素释放激素（PRLH）参与控制食物摄入。 在我最近的研究中，我发现胰高血糖素（GCG）神经元对于进餐终止特别重要。 在清醒行为小鼠中对这两种细胞类型进行的首次神经记录中，我意外地发现这些细胞。 在进餐开始时，这些技术和信号会被前馈信号迅速激活。 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：信号如何 我建议在这里解决长期能量平衡调节脑干回路来控制进餐终止的问题。 通过研究长期能量平衡的两个调节因子——刺豚鼠相关肽（AgRP）如何解决这个问题 神经元和瘦素 – 共同调节 PRLH 或 GCG 神经元动力学或它们对进食行为的控制。 这些结果将揭示长期系统如何调节脑干回路来调节膳食量，这是一个 总体食物摄入量的重要决定因素，并且在肥胖等情况下可能会失调。