Elucidating the role for MCH neurons in feeding behavior and responses to sensory food cues

阐明 MCH 神经元在进食行为和对感官食物线索的反应中的作用

• 批准号: 10272685
• 负责人: Christian Richard Burgess
• 金额: $ 43.68万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10272685
• 关键词: Adaptive Behaviors; Advertisements; Americas; Amygdaloid structure; Anatomy; Anorexia; Area; Arousal; Attention; Automobile Driving; Basic Science; Behavior; Behavioral; Brain; Brain region; Candy; Cognitive; Consummatory Behavior; Consumption; Cues; Eating; Eating Disorders; Environment; Feeding behaviors; Fiber; Financial cost; Food; Food Processing; Fostering; Future; Goals; Health; Health Care Costs; Human; Hunger; Hyperphagia; Hypothalamic structure; Injections; Investigation; Knockout Mice; Lateral; Learning; Mediating; Metabolic; Metabolism; Mission; Modeling; Modernization; Neurons; Nucleus Accumbens; Obesity; Obesity Epidemic; Palate; Pathway interactions; Phenotype; Photometry; Population; Prevalence; Process; Public Health; Rabies; Research; Rewards; Role; Sensory; Signal Transduction; Site; Sleep; Societies; Stimulus; Structure; Structure of nucleus infundibularis hypothalami; System; United States National Institutes of Health; Visual; Work; base; behavioral response; billboard; craving; feeding; food consumption; hormonal signals; imaging approach; improved; in vivo; in vivo calcium imaging; innovation; melanin-concentrating hormone; melanin-concentrating hormone receptor; neuromechanism; optogenetics; peptide hormone; relating to nervous system; response; reward processing; sensory stimulus; sleep behavior; tool; zona incerta

Project summary America has an obesity epidemic, which is getting progressively worse and has immense human and financial costs. While our understanding of homeostatic feeding circuits has advanced steadily over the past several decades much remains unclear. In addition, much of our food consumption is not due to homeostatic need, instead, it is often a result of non-homeostatic drivers. Cravings for sugary or fatty foods, even when sated, drive increased consumption. Stimuli in our environment that signal food availability, including food- associated visual cues in the form of advertisements, billboards, and candy-bar wrappers, promote these cravings, and, ultimately, promote consumption. We aim to understand the circuits that drive feeding behavior, including how food-associated sensory stimuli can hijack normally advantageous neural processes to increase consumption and contribute to the obesity epidemic. We propose to determine the role of melanin-concentrating hormone (MCH) neurons in regulating feeding and responses to food-associated cues. MCH neurons in the lateral hypothalamus and zona incerta project throughout the brain, including to limbic and higher-order brain regions, and can drive a diverse array of behaviors, such as feeding, sleep, and learning. Discrete MCH subpopulations likely serve separate functions; for example, some might promote feeding while others promote sleep or other consummatory behaviors. Our central hypothesis is that MCH neurons will drive food consumption, increase the rewarding value of consummatory behavior and enhance responses to food-associated cues through projections to the arcuate nucleus, nucleus accumbens, and basolateral amygdala. We will first identify the activity and projection profiles of MCH neuron subpopulations that drive feeding by mapping specific subpopulations of MCH neurons and recording their activity across a range of feeding behaviors. We will then activate specific MCH projections to determine if they are capable of driving feeding behaviors, in addition to other MCH-related behaviors, including sleep. We expect that a specific subpopulation of MCH neurons projecting to the nucleus accumbens and basolateral amygdala will respond to food rewards and increase consummatory behaviors. Finally, we will use in vivo two-photon calcium imaging to investigate the role for MCH activity in forming enhanced behavioral and sensory responses to food-associated cues. By using cutting-edge tools and approaches to identify the role for the MCH system in feeding behavior and responses to food cues, we will generate findings that can help to identify cognitive targets and mechanisms for treating maladaptive feeding behaviors.

项目概要 美国的肥胖症流行病日益严重，并且有大量的人口和人口。 财务成本。虽然我们对稳态喂养回路的理解在过去稳步推进 几十年来，还有很多事情尚不清楚。此外，我们的大部分食物消耗并不是由于体内平衡 相反，它通常是非稳态驱动因素的结果。对含糖或脂肪食物的渴望，即使 满足，带动消费增加。我们环境中的刺激信号表明食物供应，包括食物- 以广告、广告牌和糖果包装纸形式出现的相关视觉线索，促进这些 欲望，并最终促进消费。我们的目标是了解驱动进食行为的电路， 包括与食物相关的感官刺激如何劫持通常有利的神经过程以增加 消费并导致肥胖流行。 我们建议确定黑色素浓缩激素（MCH）神经元在调节中的作用 喂养和对食物相关线索的反应。下丘脑外侧和未定带的 MCH 神经元 投射到整个大脑，包括边缘系统和高阶大脑区域，并且可以驱动一系列不同的 行为，例如进食、睡眠和学习。离散的 MCH 亚群可能具有不同的功能； 例如，有些可能促进进食，而另一些可能促进睡眠或其他完美行为。我们的 中心假设是 MCH 神经元会驱动食物消耗，增加食物的奖励价值 通过对弓形的预测来增强对食物相关线索的反应 核、伏隔核和基底外侧杏仁核。 我们将首先确定驱动进食的 MCH 神经元亚群的活动和投射概况 通过绘制 MCH 神经元的特定亚群并记录它们在一系列进食中的活动 行为。然后，我们将激活特定的 MCH 预测，以确定它们是否能够驱动进食 行为，以及其他与 MCH 相关的行为，包括睡眠。我们预计特定的亚人群 投射到伏隔核和基底外侧杏仁核的 MCH 神经元将对食物奖励做出反应 并增加完善行为。最后，我们将使用体内双光子钙成像来研究 MCH 活动在增强对食物相关线索的行为和感官反应中的作用。经过 使用尖端工具和方法来确定 MCH 系统在喂养行为和 对食物线索的反应，我们将得出有助于确定认知目标和机制的发现 用于治疗适应不良的喂养行为。