Prefrontal cortex-hypothalmus interactions and feeding

描述（由申请人提供）：目前肥胖的“流行”被称为世界范围内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控制行为输出的方式知之甚少。因此，本研究的重点是表征内侧前额叶皮层（一个调节行为输出和情感反应的“执行”控制的大脑区域）和下丘脑底物（调节进食的稳态控制）之间的功能相互作用。我们最近发现内侧前额叶皮层（mPFC）在控制进食微观结构中的一个新颖的、特定的作用，从而提出了这一建议。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进食行为反应的方式。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如何影响下丘脑对厌氧肽和厌氧肽的反应。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的临时病变如何改变与进食相关的大脑激活（使用Fos表达测量）。与公众健康相关：这些研究有可能揭示大脑中控制决策和冲动的部分（如前额皮质）如何与根据能量需求调节食物摄入的系统相互作用，甚至可能压倒这些系统。这可能从根本上导致摄食行为失调。有趣的是，脑成像研究显示，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层的改变是如何最终转化为行为变化的。

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.