Neural Mechanisms of Prefrontal Influence on Food Intake

描述（由申请人提供）：肥胖在医疗费用和生活质量方面具有显著的后果。饮食和体重都受到基因的影响，同时对食物环境也很敏感。很明显，我们无法控制摄入量， 容易获得的食物是这一问题的核心。从本质上讲，这类似于吸毒成瘾，人们想要控制一种行为，但很难做到这一点。人类的成像数据表明，大脑皮层区域参与了这种自我调节和决策。对成瘾动物模型的研究支持前额叶皮层（PFC）在渴望和摄入中的重要作用。然而，大多数动物模型中的进食研究都没有包括皮层，主要集中在下丘脑回路上。本提案旨在通过将PFC纳入我们的进气控制视图和模型来填补这一空白。初步数据确定，PFC的多巴胺受体1型（D1）锥体神经元的光遗传学刺激足以增加食物摄入。额外的回路分析确定了基底外侧杏仁核 (BLA)作为介导这些效应的潜在靶区域。这项工作将研究这种新的D1 PFC到杏仁核回路，同时将其与已知影响进食的其他大脑区域连接起来。这项工作很重要，因为它将扩展我们的进食神经模型，并开始弥合啮齿动物和人类研究之间的差距。

DESCRIPTION (provided by applicant): Obesity has significant consequences in terms of medical cost and quality of life. Eating and body weight are both genetically influenced while also clearly sensitive to the food environment. It is clear that our inability to control intake of readily available food is central to this problem. In essence, this is similar to drug addiction where people want to control a behavior, but struggle to do so. Human imaging data implicates regions of the cortex in this type of self-regulation and decision-making. Studies in animal models of addiction support an important role for prefrontal cortex (PFC) in craving and intake. However, most studies of feeding in animal models have not included the cortex, with prominent models primarily focused on hypothalamic circuits. This proposal aims to fill in this gap by incorporating the PFC into our views and models of intake control. Preliminary data establish that optogenetic stimulation of dopamine receptor type 1 (D1) pyramidal neurons of the PFC is sufficient to increase food intake. Additional circuit analysis identifies the basolateral amygdala (BLA) as a potential target region mediating these effects. The proposed work will interrogate this novel D1 PFC to amygdala circuit while also connecting it with other brain regions that are known to influence feeding. This work is important, as it will expand our neural models of feeding and begin to bridge the gap between rodent and human studies.