Gustatory Control of Sodium Appetite

描述（由申请人提供）：奖励仍然是神经科学的核心难题。了解它的神经基础是为药物成瘾、肥胖、神经性厌食症和抑郁症等广泛疾病开发基本疗法的关键。盐的食欲是一种由身体负钠平衡引发的生物驱动，为研究奖励的核心机制提供了一个独特的模型。对钠的胃口满足了动力的所有标准，就像饥饿和口渴一样，但也有一些明显的优势。它的充分刺激很简单，那就是钠离子，而在外部环境中，这种刺激是由单一的感觉系统——味觉来传导的。大多数哺乳动物，包括人类，对钠的识别是天生的。在正常情况下，动物对弱盐水溶液表现出轻微的偏好，并积极避免强盐水。然而，当对钠有食欲时，即使是浓盐也会成为首选。这里的问题是，身体钠平衡的适度变化是如何带来这种有苦味刺激的奖励值的急剧增加的？与视觉、听觉和其他功能不同，味觉与边缘前脑有直接的神经联系，这是一个对动机和奖励的阐述至关重要的大系统。总体前提是，来自第二中枢味觉中继——桥桥臂旁核（PBN）的味觉传入活动通过这些边缘连接到达神经奖励系统，并在钠需求期间将NaCl引起的感觉信息从厌恶转化为奖励。我们已经知道，PBN的损伤会阻止Na-appetite的表达，但丘脑和皮质味觉区的损伤却不会。我们使用伏隔核释放多巴胺（DA）作为前脑奖励指数。即使在有经验的动物中，假舔蔗糖也会产生大量的伏隔核DA。在正常情况下，假性摄入0.15 M NaCl只产生一个小的DA尖峰。然而，在na -食欲期间，盐的摄入释放伏隔体DA羽，与蔗糖相媲美。基于这些事实，我们提出了三个实验挑战的整体前提。具体来说，我们将使用(1)中枢病变，(2)微透析和(3)FOS免疫组织化学来确定分布于边缘前脑的臂旁味觉神经活动对于na -食欲的表达是否必要和充分，以及这些相同的通路是否负责调节食欲期间伏隔核多巴胺的释放。要测试的特定边缘区域包括外侧下丘脑、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广谱疾病的关键，如吸毒成瘾、肥胖、神经性厌食症和抑郁症。这个项目研究奖赏的神经基础，利用味觉，因为一些味觉刺激是固有的奖励或厌恶。这项研究的目的是确定味觉神经活动是如何到达产生奖赏的大脑区域的，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.