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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

基本信息

批准号：
10666467
负责人：
Christian Richard Burgess
金额：
$ 41.91万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
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/10666467
关键词：
Adaptive Behaviors Advertisements 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 Genetic Goals Health Health Care Costs Human Hunger Hyperphagia Hypothalamic structure Injections Investigation Knockout Mice Lateral Learning Maps Mediating Metabolic Metabolism Mission Modeling Modernization Neurons Nucleus Accumbens Obesity Obesity Epidemic 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 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 neural neuromechanism optogenetics peptide hormone response reward processing sensory stimulus sleep behavior tool zona incerta

项目摘要

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.

项目总结