Prefrontal cortex-hypothalmus interactions and feeding

描述（由申请人提供）：目前肥胖的“流行病”已被称为全球主要的公共卫生问题之一。尽管最近在发现控制食物摄入的离散下丘脑肽系统方面取得了进展，但对认知/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，这项建议的重点是表征内侧前额叶皮层，大脑区域介导的“执行”控制行为输出和情感反应，和下丘脑基质介导的稳态控制喂养之间的功能相互作用。我们最近发现内侧前额叶皮层（mPFC）在控制进食微结构中的一种新的、特定的作用，这一发现为我们的建议提供了信息。我们发现，产生暂时性病变mPFC从根本上改变了大鼠组织行为反应的方式与摄食行为。我们的目的是研究与这种效果相关的行为机制和解剖学特异性，并研究如何灭活mPFC影响下丘脑给药的食欲肽和促食欲肽的反应。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的临时病变改变与进食相关的大脑激活（使用Fos表达测量）的方式。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（如前额叶皮层）如何与调节食物摄入以响应能量需求的系统相互作用，甚至可能压倒这些系统。这可能会导致饮食行为的根本失调。有趣的是，大脑成像研究显示，前额叶皮层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层改变最终如何转化为行为变化。

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.