Prefrontal cortex-hypothalamus interactions and feeding

前额皮质-下丘脑相互作用和进食

基本信息

批准号：
7540994
负责人：
BRIAN A BALDO
金额：
$ 29.77万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-01-15 至 2011-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7540994
关键词：
Address Affective Agonist Area Behavior Behavior Control Behavioral Behavioral Mechanisms Brain Brain imaging Brain region Cannulations Cognitive Complex Data Decision Making Dose Eating Eating Disorders Environment Epidemic Feeding behaviors Food Glutamate Receptor Goals Hypothalamic structure Impulsivity Intake Lateral Lead Leptin Lesion Maps Measures Medial Mediating Muscimol Neurons Nucleus Accumbens Obesity Output Peptides Peripheral Prefrontal Cortex Process Public Health Rattus Research Personnel Rewards Role Signal Transduction Site Specificity Structure Structure of terminal stria nuclei of preoptic region System Taste Perception Testing Time Time Study Translating Work cognitive system drinking energy balance executive function feeding ghrelin information processing interest melanocortin receptor mind control neuropeptide Y novel orofacial programs receptor research study response stem

项目摘要

DESCRIPTION (provided by applicant): The current 'epidemic' of obesity has been called one of the leading public health concerns worldwide. Despite recent progress in the discovery of discrete hypothalamic peptide systems that control food intake, little is known about the manner in which cognitive/affective processing coordinates with hypothalamic energy balance systems to control behavioral output. Hence, this proposal focuses on characterizing functional interactions between the medial prefrontal cortex, a brain region mediating 'executive' control over behavioral output and affective responses, and hypothalamic substrates mediating the homeostatic control of feeding. This proposal is informed by our recent discovery of a novel, specific role of medial prefrontal cortex (mPFC) in controlling feeding microstructure. We find that producing temporary lesions in mPFC fundamentally alters the manner in which rats organize behavioral responses with respect to ingestive behavior. We aim to investigate the behavioral mechanisms and anatomical specificity associated with this effect, and to examine how inactivating mPFC influences the response to hypothalamic administration of orexigenic and anorexic peptides. To obtain a functional anatomical correlate of these behavioral studies, we will investigate the manner in which temporary lesions of the mPFC alter brain activation (measured using Fos expression) associated with feeding. Relevance to public health: These studies have the potential to reveal how the parts of the brain controlling decision-making and impulsivity (such as the prefrontal cortex) can interact with, and perhaps overwhelm, the systems that regulate food intake in response to energy needs. This could lead to fundamentally dysregulated feeding behavior. It is interesting that brain imaging studies have shown alterations in prefrontal cortex function in association with eating disorders and obesity. Our work may help understand how these cortical alterations are ultimately translated into behavioral changes.

描述（由申请人提供）：当前的肥胖“流行病”被称为全球主要的公共卫生问题之一。尽管最近在控制食物摄入的离散下丘脑肽系统的发现方面取得了进展，但人们对认知/情感处理与下丘脑能量平衡系统协调以控制行为输出的方式知之甚少。因此，该提案重点关注内侧前额叶皮层（介导行为输出和情感反应“执行”控制的大脑区域）与介导进食稳态控制的下丘脑基质之间的功能相互作用。我们最近发现了内侧前额叶皮层（mPFC）在控制摄食微观结构中的一种新颖的、特定的作用，从而为这一提议提供了依据。我们发现，在 mPFC 中产生暂时性损伤从根本上改变了大鼠组织与摄取行为相关的行为反应的方式。我们的目的是研究与这种效应相关的行为机制和解剖学特异性，并研究失活的 mPFC 如何影响下丘脑对促食欲和厌食肽给药的反应。为了获得这些行为研究的功能解剖学相关性，我们将研究 mPFC 的暂时损伤如何改变与进食相关的大脑激活（使用 Fos 表达测量）。与公共卫生的相关性：这些研究有可能揭示大脑中控制决策和冲动的部分（例如前额叶皮层）如何与调节食物摄入量以响应能量需求的系统相互作用，甚至可能压倒这些系统。。这可能会导致进食行为从根本上失调。有趣的是，大脑成像研究表明前额皮质功能的改变与饮食失调和肥胖有关。我们的工作可能有助于理解这些皮质改变如何最终转化为行为变化。