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

项目摘要 美国有一个肥胖流行病，这是越来越严重，并有巨大的人类和 财务费用。虽然我们对自我平衡进食回路的理解在过去已经稳步推进， 几十年来，仍有许多问题不清楚。此外，我们的大部分食物消耗不是由于体内平衡 相反，它往往是非稳态驱动程序的结果。对含糖或高脂肪食物的渴望，即使 满足，带动消费增长。我们环境中的刺激物，标志着食物的可用性，包括食物- 广告、广告牌和糖果包装纸等形式的相关视觉提示， 消费，最终促进消费。我们的目标是了解驱动进食行为的电路， 包括食物相关的感官刺激如何劫持正常有利的神经过程， 消费和促进肥胖流行。 我们建议确定黑色素浓集激素（MCH）神经元在调节 进食和对食物相关线索的反应。下丘脑外侧部和齿状回的MCH神经元 投射到整个大脑，包括边缘系统和更高级的大脑区域，并可以驱动各种各样的 行为，如进食、睡眠和学习。离散的妇幼保健亚群可能发挥不同的功能; 例如，一些可能促进进食，而另一些则促进睡眠或其他消费行为。我们 中心假设是，MCH神经元将驱动食物消费，增加奖励价值， 完善的行为，并通过对弓状核的投射增强对食物相关线索的反应 核、杏仁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喂养 行为，以及其他与妇幼保健有关的行为，包括睡眠。我们认为一个特定的亚群 投射到杏仁核和基底外侧杏仁核的MCH神经元对食物奖赏有反应 并增加消费行为。最后，我们将使用在体双光子钙成像来研究 MCH活性在形成对食物相关线索的增强的行为和感觉反应中的作用。通过 使用先进的工具和方法来确定妇幼保健系统在喂养行为中的作用， 反应的食物线索，我们将产生的发现，可以帮助确定认知目标和机制 用于治疗适应不良的进食行为

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.