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

项目总结 美国有一种肥胖症的流行，这种流行病正在变得越来越严重，而且有大量的人类和 财务成本。虽然我们对动态平衡馈电回路的理解在过去一直在稳步推进 几十年来，许多事情仍不明朗。此外，我们的大部分食物消费并不是由于动态平衡 相反，需求往往是非稳态驱动因素的结果。对含糖或高脂肪食物的渴望，即使在 满足了，推动了消费的增加。我们环境中发出食物供应信号的刺激，包括食物- 广告、广告牌和糖果棒包装等形式的相关视觉提示，促进了这些 渴望，并最终促进消费。我们的目标是了解驱动觅食行为的电路， 包括食物相关的感觉刺激如何劫持通常有利的神经过程以增加 消费，并导致肥胖症流行。 我们建议确定黑色素浓缩激素(MCH)神经元在调节 摄食和对食物相关线索的反应。下丘脑外侧区和未定带内的MCH神经元 投射到整个大脑，包括边缘和更高级别的大脑区域，并可以驱动各种不同的 行为，如进食、睡眠和学习。离散的妇幼保健亚群可能具有不同的功能； 例如，一些人可能会促进进食，而另一些人可能会促进睡眠或其他消费行为。我们的 中心假说是，MCH神经元将推动食物消费，增加 通过向弓状核的投射增强对食物相关线索的反应 核团、伏隔核和基底外侧杏仁核。 我们将首先确定驱动摄食的MCH神经元亚群的活动和投影分布 通过绘制特定的MCH神经元亚群并记录它们在一系列摄食过程中的活动 行为。然后，我们将激活特定的妇幼保健投射，以确定它们是否能够驱动喂养 行为，以及其他与母婴健康相关的行为，包括睡眠。我们预计有一个特定的亚群 投射到伏隔核和杏仁基底外侧核的MCH神经元将对食物奖励做出反应 并增加消费行为。最后，我们将使用体内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官反应中的作用。通过 使用尖端工具和方法确定妇幼保健系统在喂养行为和 对食物提示的反应，我们将产生有助于识别认知目标和机制的发现 用于治疗不适应的喂养行为。

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.