Signals to Feed: Biological and Associative Mechanisms

一种由来已久的观点是，能量摄入和体重的调节依赖于综合控制 通过环境中与食物有关的外部线索和从内部环境中产生的生理信号。在……里面 事实上，根据几种说法，这种环境食物的暗示能够唤起食欲和 知觉反应受制于抑制这些行为的感觉间饱腹感信号。在 在这个框架中，能量失调导致肥胖可以被视为内感饱腹感线索的失败 充分应对环境中食物暗示引起的反应。这种类型的失败很可能会 成为所谓的“肥胖”环境的重要贡献者。研究的目的 在本申请中提出的目的是阐明导致和支持以下问题的因素 相对于外部食物相关刺激的控制，内部刺激对食欲行为的控制减弱。 基于我们实验室和其他地方最近的研究，我们认为环境保护的能力 唤起进食的线索和抑制摄入的生理线索的能力取决于学习和 记忆。然而，这两种类型的线索涉及不同类型的学习和记忆过程，这些过程依赖于 与食欲的抑制相比，不同的大脑结构和回路参与了食欲的唤起 和完美化的行为。我们计划进行的研究将评估一个具体的、机械的和可测试的 这解释了食用高饱和脂肪和高糖分的饮食(也就是。“西式饮食”)可以 扰乱海马体的功能和生理(一种大脑结构，长期以来被认为是学习和 内存)。这些干扰降低了内部饱腹感信号抑制由 环境中与食物有关的信号。本申请中计划的研究将促进对以下方面的了解 这种机制的运作，以及它的神经底物，在雄性和雌性大鼠身上都会 研究这一模式对预防过量摄入和身体健康的干预措施的影响。 服用WD后体重增加，恢复正常调节功能。

A longstanding idea is that the regulation of energy intake and body weight depends on the integrative control by external food-related cues in the environment and physiological signals arising from the internal milieu. In fact, according to several accounts the ability of such environmental food cues to evoke appetitive and consummatory responding is held in check by interoceptive satiety signals that inhibit those behaviors. Within this framework, energy dysregulation leading to obesity can be seen as a failure of interoceptive satiety cues to adequately counter response evocation by food cues in the environment. This type of failure would presumably be an important contributor to what has been termed the “obesogenic” environment. The purpose of research proposed in this application is to elucidate the factors that contribute, to and the mechanisms that underlie, the weakening of internal stimulus control of appetitive behavior relative to control by external food-related stimuli. Based on recent research from our laboratory and elsewhere, we propose that both the ability of environmental cues to evoke eating and the ability of physiological cues to inhibit intake are dependent on learning and memory. However, both types of cues involve different types of learning and memory processes that rely on distinct brain structures and circuits are involved with the evocation, compared to the inhibition, of appetitive and consummatory behavior. The research we plan to do will evaluate a specific, mechanistic, and testable account that explains how consuming a diet high in saturated fat and sugar (a.k.a. “Western diet” (WD)) can disturb the function and physiology of the hippocampus (a brain structure long-identified with learning and memory). These disturbances reduce the ability of internal satiety signals to inhibit eating behavior evoked by signals in the environment related to food. Research planned in this application will advance knowledge about the operation of this mechanism, along with its neural substrates, in both male and female rats and will investigate the implications of this model for interventions that could both prevent excess intake and body weight gain and restore normal regulatory function following consumption of WD.