Elucidating MCH neural circuitry underlying consummatory behavior
阐明完成行为背后的 MCH 神经回路
基本信息
- 批准号:10600482
- 负责人:
- 金额:$ 4.02万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-05-01 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:AffectAmygdaloid structureAnatomyAnimalsAppetite RegulationAreaArousalBasic ScienceBehaviorBehavioralBehavioral ParadigmBody WeightBrainCerebral cortexComplexConsummatory BehaviorConsumptionDecision MakingDiseaseDissociationEatingEating DisordersEquilibriumFeeding behaviorsFinancial costFoodFood Intake RegulationFosteringFutureGoalsHealthHealth Care CostsHeterogeneityHumanHypothalamic structureInfusion proceduresInterventionLateralLearningMapsMediatingMetabolicMissionModernizationMotivationMusNeuronsNoseNucleus AccumbensNutrientNutritionalObesityPatternPhenotypePhysiologicalPopulationPrevalencePropertyPublic HealthREM SleepResearchRewardsRoleSelf StimulationSleepSocietiesStructure of nucleus infundibularis hypothalamiSystemTherapeuticUnited StatesUnited States National Institutes of HealthWorkcravingdiet and exerciseexperienceexperimental studyfeedingfood consumptiongraspimprovedinnovationlocus ceruleus structuremelanin-concentrating hormoneneuralneural circuitneuromechanismnew therapeutic targetoptogeneticspeptide hormonesleep behaviorzona incerta
项目摘要
Project Summary/Abstract
Eating disorders and obesity are becoming increasingly severe in the United States, posing extensive
health and financial costs to those affected. Current treatments focus heavily on changes to diet and exercise,
with few interventions available targeting the neural circuitry underlying these disorders. The last few decades
of research have advanced our understanding of homeostatic feeding circuits, although much remains unclear.
Furthermore, homeostatic need is not the sole factor in the decision to consume food. Humans commonly
experience non-homeostatic motivators to eat, such as craving of sugary or fatty foods even when sated (i.e.,
“there is always room for dessert”). Neural representations of food availability and desirability are crucial in our
decision-making surrounding consumption. Neural circuits responsible for motivation and reward can promote
eating in the absence of nutritional deficit or homeostatic necessity, resulting in obesity or other eating disorders.
The goal of this work is to understand the neural circuits that drive feeding behavior, including both homeostatic
and non-homeostatic drives to feed.
Melanin-concentrating hormone (MCH) neurons are a relevant target for both homeostatic and non-
homeostatic motivators to eat. MCH neurons originate in the lateral hypothalamus and zona incerta, and project
to many areas throughout the brain, including feeding/reward areas like the nucleus accumbens (NAcc) and the
arcuate nucleus (ARC), as well as arousal areas like the locus coeruleus (LC). Interestingly, MCH neurons have
been implicated in a diverse array of behaviors including feeding, sleep, and learning. We hypothesize that
discrete MCH subpopulations promote specific behaviors via projections to different downstream areas.
Specifically, we hypothesize that MCH projections to NAcc or ARC will promote feeding and not sleep, while
MCH projections to LC will promote sleep and not feeding.
This proposal aims to isolate the behavioral functions of specific MCH subpopulations by optogenetic
activation of MCH neuron terminals in discrete downstream areas (NAcc, ARC, LC). Using optogenetic
stimulation in combination with rigorous behavioral paradigms, observing both feeding and sleep behaviors, this
work will reveal how the MCH system promotes feeding in the absence of effects on arousal state. Furthermore,
this proposal aims to elucidate the motivational valence of MCH neuron activity, as well as its involvement with
homeostatic and non-homeostatic feeding, by allowing mice to voluntarily self-stimulate discrete MCH
projections with or without paired food delivery. By using cutting-edge approaches and behavioral analysis to
identify the role of MCH circuitry in feeding behaviors, we will increase understanding of the neural circuitry
behind maladaptive feeding and help to identify novel therapeutic targets for the treatment of eating disorders
and obesity.
项目总结/文摘
项目成果
期刊论文数量(0)
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Katherine L Furman其他文献
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