Prefrontal cortex-hypothalmus interactions and feeding

前额皮质-下丘脑相互作用和进食

• 批准号: 7340470
• 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
• 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/7340470
• 关键词: Address; Affective; Agonist; Appetitive Behavior; Area; Behavior; Behavior Control; Behavioral; Behavioral Mechanisms; Brain; Brain imaging; Brain region; Cannulations; Cognitive; Complex; Computer information processing; 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; interest; melanocortin receptor; mind control; neuropeptide Y; novel; orofacial; programs; receptor; research study; response; stem

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）：肥胖的当前“流行病”被称为全球领先的公共卫生问题之一。尽管在控制食物摄入的离散下丘脑肽系统的发现最近进展，但对与下丘脑能量平衡系统控制行为输出的认知/情感加工坐标的方式知之甚少。因此，该提案的重点是表征内侧前额叶皮层之间的功能相互作用，前额叶皮层，一个大脑区域，介导了对行为产量和情感反应的“执行”控制，以及介导饲料稳态控制的下丘脑底物。我们最近发现了内侧前额叶皮层（MPFC）在控制喂养微观结构中的新颖，特定的作用来告知该建议。我们发现，在MPFC中产生临时病变从根本上改变了大鼠在摄入行为方面组织行为反应的方式。我们的目的是研究与这种作用相关的行为机制和解剖学特异性，并研究MPFC如何影响对甲状腺素和厌食肽下丘脑给药的反应。为了获得这些行为研究的功能解剖相关性，我们将研究MPFC的临时病变改变与喂养相关的临时病变改变脑激活（使用FOS表达）。与公共卫生的相关性：这些研究有可能揭示大脑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响应能源需求的系统相互作用，也许是压倒性的。这可能导致根本上调节的喂养行为。有趣的是，大脑成像研究表明，前额叶皮层功能与饮食失调和肥胖有关。我们的工作可能有助于了解这些皮质改变最终如何转化为行为改变。