Gustatory Control of Sodium Appetite

描述(申请人提供)：奖励仍然是神经科学的中心难题。了解它的神经基础是开发治疗一系列疾病的基本原理的关键，这些疾病包括药物成瘾、肥胖、神经性厌食症和抑郁症。食盐是由体内负钠平衡触发的生物动力，这为研究中枢奖赏机制提供了一个独特的模型。钠的胃口符合所有的动机标准，饥饿和口渴也是如此，但也有一些明显的优势。它充分的刺激是简单的，钠离子，在外部环境中，这种刺激是由单一的感觉系统传递的，味觉。在大多数哺乳动物中，包括人类，对钠的识别是与生俱来的。在正常情况下，动物充其量会表现出对弱盐水溶液的温和偏好，并积极避免强盐水溶液。然而，当出现钠的胃口时，即使是浓盐也变得非常受欢迎。这里的问题是，身体钠平衡的适度变化如何带来这种智慧刺激的奖励价值的戏剧性增加？与视觉、试听和一些论文不同，味觉与边缘前脑有直接的神经联系，边缘前脑是一个对阐述动机和奖励至关重要的大系统。总的前提是，来自第二中枢味觉传递的味觉传入活动桥臂旁核(PBN)通过这些边缘连接到达神经奖赏系统，并在钠需要时将由氯化钠引起的感觉信息从厌恶转变为奖赏。我们已经知道，PBN的损伤可以阻止Na-食欲的表达，但丘脑和皮质味觉区域的损伤不会。我们使用伏隔核多巴胺(DA)的释放作为前脑的奖赏指数。即使在有经验的动物身上，假舔蔗糖也会产生大量的伏隔核多巴胺外流。在正常情况下，假摄入0.15M的氯化钠只会产生一个小的DA峰.然而，在纳食欲期间，盐的摄入会释放出与蔗糖相当的伏隔膜DA羽毛。基于这些事实，我们对总体前提提出了三个实验挑战。具体地说，我们将使用(1)中央损毁，(2)微透析，和(3)FOS免疫组织化学来确定通过边缘前脑分布的臂旁味觉神经活动是否对Na-食欲的表达是必要和充分的，以及这些相同的通路是否负责调节食欲期间伏隔多巴胺的释放。要测试的特定边缘区域包括下丘脑外侧、杏仁核和终纹床核。快乐是大脑活动的产物。了解快乐或奖励的神经基础是开发合理治疗各种疾病的关键，这些疾病包括药物成瘾、肥胖、神经性厌食症和抑郁症。这个项目使用味觉来研究奖励的神经基础，因为一些味觉刺激本身就是奖励或厌恶的。研究的目标是确定味觉神经活动如何到达产生奖励的大脑区域，以及这种感觉信息在这个过程中是如何转化的。

DESCRIPTION (provided by applicant): Reward remains a central puzzle of neuroscience. Understanding its neural bases is key in developing rationale therapies for a broad spectrum of maladies such as drug addiction, obesity, anorexia nervosa, and depression. Salt appetite is a biological drive triggered by a negative body sodium balance that offers a unique model for investigating the central mechanisms of reward. Sodium appetite fulfills all of the criteria for motivation, as do hunger and thirst, but has some distinct advantages. Its adequate stimulus is simple, the sodium ion, and in the external environment, this stimulus is transduced by a single sensory system, taste. In most mammals, including humans, recognition of sodium is innate. Under normal circumstances, animals show at best a mild preference for weak saline solutions and actively avoid strong ones. When a Na-appetite arises, however, even strong salt becomes highly preferred. The question here is how a modest shift in body sodium balance brings about a dramatic increase in the reward value of this sapid stimulus? Unlike vision, audition, and somethesis, taste has direct neural connections with the limbic forebrain, a large system that is critical to the elaboration of motivation and reward. The overall premise is that gustatory afferent activity from the second central gustatory relay, pontine parabrachial nucleus (PBN), reaches neural reward systems via these limbic connections and, during sodium need, transforms the sensory message elicited by NaCl from aversive to rewarding. We already know that lesions of the PBN prevent the expression of Na-appetite, but that damage to the thalamic and cortical gustatory areas does not. We use the release of dopamine (DA) in the nucleus accumbens as a forebrain index of reward. Sham licking sucrose produces a substantial efflux of accumbens DA even in experienced animals. Under normal circumstances, sham intake of 0.15 M NaCl produces only a small DA spike. During Na-appetite, however, salt intake releases an accumbens DA plume rivaling that of sucrose. Based on these facts, we propose three experimental challenges to the overall premise. Specifically, we will use (1) central lesions, (2) microdialysis, and (3) FOS immunohistochemistry to determine if parabrachial gustatory neural activity distributed via the limbic forebrain is necessary and sufficient for the expression of a Na-appetite, and if these same pathways are responsible for modulating the release of accumbens dopamine during the appetite. The specific limbic areas to be tested include the lateral hypothalamus, the amygdala, and the bed nucleus of the stria terminalis. Pleasure is a product of brain activity. Understanding the neural bases of pleasure or reward is key in developing rational therapies for in broad spectrum of maladies such as drug addiction, obesity, anorexia nervosa, and depression. This project investigates the neural bases of reward using the sense of taste because some gustatory stimuli are inherently rewarding or aversive. The research goal is to determine how taste neural activity reaches brain areas that produce reward and how this sensory information is transformed in the process.