Prefrontal cortex-hypothalamus interactions and feeding

描述(申请者提供)：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，但人们对认知/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，这项建议侧重于描述内侧前额叶皮质和下丘脑底物之间的功能相互作用。内侧前额叶皮质是大脑中的一个区域，负责调节对行为输出和情感反应的执行控制，而下丘脑基质则负责调节摄食的动态平衡控制。我们最近发现了内侧前额叶皮质(MPFC)在控制摄食微结构中的一个新的、特定的作用，这一建议得到了启发。我们发现，在mPFC产生暂时性损害从根本上改变了大鼠组织与摄食行为有关的行为反应的方式。我们的目标是研究与这一效应相关的行为机制和解剖学特异性，并研究灭活mPFC如何影响下丘脑给予食欲素和厌食性肽的反应。为了获得这些行为研究的功能解剖学相关性，我们将调查mPFC的暂时性损害改变与摄食相关的大脑激活(使用Fos表达测量)的方式。与公共健康相关：这些研究有可能揭示大脑中控制决策和冲动的部分(如前额叶皮质)如何与调节食物摄入量以回应能量需求的系统相互作用，甚至可能压倒它们。这可能会导致从根本上不规范的喂养行为。有趣的是，大脑成像研究表明，前额叶皮质功能的变化与进食障碍和肥胖有关。我们的工作可能有助于理解这些皮质变化最终是如何转化为行为变化的。

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.