Sensory Coding in Taste

描述(由申请人提供)：胃肠道决定在许多人类疾病中起着关键作用，包括肥胖、糖尿病、厌食症、高血压和冠状动脉疾病。味觉是调节这些摄食决定的最重要因素，因此对人类健康起着重要作用。过去几十年进行的研究表明，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互惠联系。味觉也被证明参与了奖励系统，这个系统的功能障碍可能会导致暴饮暴食和肥胖。然而，味觉信息参与奖赏和摄取大脑区域的确切途径尚不清楚。臂旁核(PBN)是脑干中的关键中继核，味觉信息通过几条上升通路分流到参与感觉辨别、学习、摄取和内脏处理以及奖赏的前脑部位。对这一方案的研究将检验以下假设：从PBN到腹侧被盖区(VTA)的投射介导味觉诱发的奖励，而从PBN到下丘脑外侧(LH)的投射介导味觉诱发的摄取。我们将使用补充的解剖学、生理学和行为学技术的组合来解决这一假设。我们提出了以下具体目标：目标1：味觉PBN在小鼠体内的功能组织。我们将收集全面的规范数据，在野生型和味觉受损小鼠中建立这一关键核的组织。目标2：从PBN到VTA的直接投射是否介导了味觉诱发的奖赏？这一假说将首先用轨迹追踪和味觉诱发的FOS样免疫反应(FLI)技术进行评估：我们将调查VTA投射神经元是否在完整或味盲的小鼠中优先被甜味、奖赏刺激激活。我们还将使用活体记录技术对投射到VTA的味觉神经元进行生理学表征。最后，我们将通过将该区域的损伤与行为分析相结合，来检验VTA对于正常的奖赏是必不可少的，而不是味觉功能的假设。在目标3中，我们将使用一套类似的方法来解决这样的假设，即从PBN到LH的直接投射介导了味觉诱发的摄取，包括轨迹跟踪和味觉诱发的FLI、体内生理学以及随后的行为测量。我们将在这些实验中利用味盲Trpm5基因缺失的小鼠，以区分味觉和摄食后反馈的影响。 公共卫生相关性：消化决定在许多人类疾病中起着关键作用，包括肥胖、糖尿病、厌食症、高血压和冠状动脉疾病。味觉是调节这些摄食决定的最重要因素，因此对人类健康起着重要作用。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.