Neural Systems of Ingestive Behavior

描述（由申请人提供）：肥胖的发生是因为个人经常摄入更多的热量比他们消耗。当食物的奖励值大于肠道中产生的饱腹感信号的总和时，就会发生这种情况。然而，赋予味觉享乐价值的神经机制仍然未知。决定是否摄取或拒绝食物的神经基质在脑干中完成。在大鼠中，脑干包含用于味觉和迷走内脏传入系统的第一和第二中枢中继，负责摄食行为的运动神经元，以及足够的整合能力来做出这一决定。然而，控制进食需要前脑的连接和前脑的连接，因为前脑与脑干的连接断开会消除自主进食。概括地说，这项研究的目标是了解前脑如何与这些后脑机制相互作用，以实现对大鼠和人类等杂食动物特征的进食行为的平滑，细致入微的控制。该项目将使用行为、神经解剖学、神经化学和电生理分析来测试有关味觉刺激的奖励值如何在大脑中阐述的假设。第一个目的是进一步确定特定的腹侧前脑预测臂旁核是至关重要的调节多巴胺的释放作为一个功能的奖励（和厌恶）性质的味觉刺激。目的2通过比较在稳态和享乐摄入过程中杏仁核和杏仁核中央核（前脑奖励系统中的假定节点）中多巴胺的释放，阐明了这些连接的功能相关性。目的3集中在脑桥味觉中继味觉神经活动，同时改变口腔和口后味觉刺激。这些发现将有助于理解基本的调节机制，这些机制无法控制由于现代饮食的适口性增强而增加的刺激而易患饮食性肥胖的个体的摄入量。

DESCRIPTION (provided by applicant): Obesity occurs because individuals regularly ingest more calories than they expend. This takes place when the reward value of the food is greater than the sum of the satiety signals arising in the gut. Nevertheless, the neural mechanisms that assign hedonic value to taste remain unknown. The neural substrates for the decision to whether ingest or reject a food are complete in the brainstem. In rats, the brainstem contains the first and second central relays for both the gustatory and vagal visceral afferent systems, the motoneurons responsible for ingestive behavior, and sufficient integrative capacity to make this decision. Nevertheless, control of ingestion requires connections to and from the forebrain because disconnecting it from the brainstem eliminates voluntary eating. Writ large, the goal of this research is to understand how the forebrain interacts with these hindbrain mechanisms to bring about the smooth, nuanced control of feeding behavior that characterizes omnivores such as rats and humans. Using behavioral, neuroanatomical, neurochemical, and electrophysiological analysis, this project will test hypotheses about how the reward value of gustatory stimuli is elaborated in the brain. The first Aim is to further determine the specific ventral forebrain projections from the parabrachial nuclei that are critical for modulating dopamine release as a function of the rewarding (and aversive) properties of taste stimuli. Aim 2 addresses functional correlates of those connections by comparing dopamine release in the nucleus accumbens and the central nucleus of the amygdala -- putative nodes in the forebrain reward system -- during homeostatic and hedonic ingestion. Aim 3 focuses on gustatory neural activity in the pontine taste relays while varying both oral and postoral taste stimulation. The findings will aid in understanding basic regulatory mechanisms that fail to control intake in individuals susceptible to developing dietary obesity due to increased stimulation from augmented palatability of the modern diet.