Sensory Coding in Taste

描述（由申请人提供）：摄食决定在许多人类疾病中起关键作用，包括肥胖、糖尿病、厌食、高血压和冠状动脉疾病。味觉是调节这些摄取决定的最重要因素，因此在人类健康中起着重要作用。过去几十年的研究表明，大脑中的味觉中心与参与体内平衡和摄取的大脑区域有直接的相互联系。味觉也被证明参与了奖励系统，而这个系统的功能障碍可能会导致暴饮暴食和肥胖。然而，味觉信息参与奖励和摄食脑区的确切途径尚不清楚。臂旁核（PBN）是脑干中的一个关键中继，味觉信息通过几条上行通路到达涉及感觉辨别、学习、摄入和内脏处理以及奖励的前脑部位。本研究的目的是验证PBN向腹侧被盖区（VTA）的投射介导味觉诱发的奖赏效应，以及PBN向外侧下丘脑（LH）的投射介导味觉诱发的摄食效应的假说。我们将使用互补的解剖学，生理学和行为技术的组合来解决这个假设。我们提出以下具体目标：目的1：味觉PBN在小鼠的功能组织。我们将收集全面的规范性数据，在野生型和味觉受损小鼠中建立该关键核的组织。目的2：从PBN到VTA的直接投射是否介导味觉诱发的奖赏？这一假设将首先进行评估与道跟踪和味觉诱发的fos样免疫反应性（FLI）技术：我们将调查是否VTA投射神经元激活优先甜味，奖励刺激在完整或味觉盲小鼠。我们也将在生理学上描述味觉神经元投射到腹侧被盖区的特性。最后，我们将测试的假设，即腹侧被盖区是必不可少的正常奖励，但不是味觉功能，通过结合这方面的病变与行为分析。在目标3中，我们将使用一组类似的方法来解决这一假设，即从PBN到LH的直接投射介导味觉诱发的摄入，包括道追踪和味觉诱发的FLI，体内生理学，以及LH病变，然后测量行为。我们将在这些实验中使用味觉盲trpm5缺失小鼠，以分离味觉与摄食后反馈的影响。 公共卫生相关性：摄食决定在许多人类疾病中起关键作用，包括肥胖、糖尿病、厌食、高血压和冠状动脉疾病。味觉是调节这些摄取决定的最重要因素，因此在人类健康中起着重要作用。这项研究的目的是阐明大脑中将味觉与进食和奖励联系起来的通路。

DESCRIPTION (provided by applicant): Ingestive decisions play a key role in a number of human conditions including obesity, diabetes, anorexia, hypertension, and coronary artery disease. The sense of taste is the most important factor in regulating these ingestive decisions, and therefore plays an important role in human health. Research conducted over the last few decades shows that taste centers in the brain have direct reciprocal connections with brain areas involved in homeostasis and ingestion. Taste has also been shown to engage the reward system, and dysfunction in this system may lead to overeating and obesity. However, the exact route whereby taste information engages reward and ingestive brain areas is unclear. The parabrachial nucleus (PBN) is a critical relay in the brainstem where gustatory information diverges via several ascending pathways to access forebrain sites involved in sensory discrimination, learning, intake and visceral processing, as well as reward. The studies of this proposal will test the hypotheses that a projection from the PBN to the ventral tegmental area (VTA) mediates taste-evoked reward, and a projection from the PBN to the lateral hypothalamus (LH) mediates taste-evoked ingestion. We will use a combination of complementary anatomical, physiological, and behavioral techniques to address this hypothesis. We propose the following specific aims: Aim 1: Functional organization of the gustatory PBN in mice. We will collect comprehensive normative data establish the organization of this key nucleus in wild type and taste-impaired mice. Aim 2: Does a direct projection from the PBN to the VTA mediate taste-evoked reward? This hypothesis will be first be evaluated with tract tracing and taste-evoked fos-like immunoreactivity (FLI) techniques: We will investigate whether or not VTA-projecting neurons are activated preferentially by sweet-tasting, rewarding stimuli in intact or taste-blind mice. We will also physiologically characterizing taste neurons that project to VTA using in vivo recording techniques. Finally, we will test the hypothesis that the VTA is essential for normal reward, but not taste function, by combining lesions of this area with behavioral analysis. In Aim 3, we will use a similar set of approaches to address the hypothesis that a direct projection from the PBN to the LH mediates taste-evoked ingestion, including tract tracing and taste-evoked FLI, in vivo physiology, and lesions of LH followed by measurement of behavior. We will utilize taste-blind trpm5 null mice in these experiments in order to separate effects of taste vs. post-ingestive feedback. PUBLIC HEALTH RELEVANCE: Ingestive decisions play a key role in a number of human conditions including obesity, diabetes, anorexia, hypertension, and coronary artery disease. The sense of taste is the most important factor in regulating these ingestive decisions, and therefore plays an important role in human health. The goal of this research is to elucidate pathways in the brain that link taste to feeding and reward.