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

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.