Corticostriatal-hypothalamic circuitry and food reward

描述（由申请人提供）：肥胖目前是美国主要的公共卫生问题之一。超过65%的美国成年人超重。肥胖使个体面临许多疾病的相当大的风险，如心脏病、高血压、糖尿病、中风和某些类型的癌症。虽然有许多复杂的因素导致了这一趋势，如遗传易感性、缺乏运动、生活方式的改变和经济因素，但大量和过度食用高热量食物（如脂肪和糖果）是主要原因。食物的摄入是生存所必需的，然而过多的高能量食物实际上已经导致了威胁生存的条件。在过去的十年中，特定的大脑和外周系统参与食欲控制，特别是在下丘脑，已经被发现和表征。然而，对于涉及情绪调节、执行功能和行为有意识控制的大脑网络如何与下丘脑能量平衡感知系统相互作用，人们知之甚少。这似乎是肥胖研究的一个重要领域，因为认知控制、决策和与进食欲望相关的情绪反应调节是控制人类食欲的主要决定因素。我们的工作重点是伏隔核（腹侧纹状体内的一个区域）在控制食物动机和食物奖励中的作用。我们已经证明了两个主要的系统，一个由内源性阿片肽控制，另一个由氨基酸（GABA和谷氨酸）受体控制，通过与外侧下丘脑和其他前脑和脑干区域的连接来控制摄取行为的某些方面。我们的目标是扩大这些研究，以研究皮层系统（即杏仁核，味觉皮层和前额叶皮层）如何与腹侧纹状体和下丘脑相互作用，在摄食行为的调节。我们将采用行为学、药理学、神经解剖学和分子方法，在一个综合的跨学科框架内解决这个问题。

DESCRIPTION (provided by applicant): Obesity is currently one of the major public health problems in the United States. Over 65% of the U.S. adult population is overweight. Obesity puts individuals at considerable risk for many disorders, such as heart disease, hypertension, diabetes, stroke, and certain types of cancer. Although there are a number of complex factors contributing to this trend, such as genetic predisposition, inactivity, lifestyle changes, and economic factors, the abundance and over consumption of calorically dense foods such as fats and sweets is largely responsible. Ingestion of food is required for survival, yet overabundance of energy-dense food has led to conditions that actually threaten survival. In the past decade, specific brain and peripheral systems involved in appetite control, particularly within the hypothalamus, have been discovered and characterized. However, relatively little is known about how brain networks involved in emotional regulation, executive function, and conscious control of behavior interact with hypothalamic energy balance-sensing systems. This would seem an important area of obesity research, as cognitive control, decision-making, and modulation of emotional responses in relation to the desire to eat are major determinants for the control of appetite in humans. Our work focuses on the role of the nucleus accumbens, a region within the ventral striatum, in the control of food motivation and food reward. We have shown that two main systems, one governed by endogenous opioid peptides and one by amino acid (GABA and glutamate) receptors, control certain aspects of ingestive behavior via connections with the lateral hypothalamus and other forebrain and brainstem regions. We aim to expand these investigations to study how cortical systems (i.e. the amygdala, gustatory cortex and prefrontal cortex) interact with ventral striatum and hypothalamus in the regulation of ingestive behavior. We will employ behavioral, pharmacological, neuroanatomical and molecular methodologies to address this question within an integrated, interdisciplinary framework.