Sensory Coding in Taste

描述（由申请人提供）：摄取决定在许多人类疾病中发挥关键作用，包括肥胖，糖尿病，厌食症，高血压和冠状动脉疾病。味觉是调节这些摄入决定的最重要因素，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大脑中涉及体内平衡和摄入的区域有着直接的相互联系。味觉也被证明与奖励系统有关，而该系统的功能障碍可能导致暴饮暴食和肥胖。然而，味觉信息参与大脑奖励和摄取区域的确切途径尚不清楚。臂旁核（PBN）是脑干中的一个重要中继，味觉信息通过几个上行通路发散到前脑参与感觉辨别、学习、摄入和内脏处理以及奖励的部位。本研究将验证从PBN到腹侧被皮层（VTA）的投射介导味觉诱发的奖赏，以及从PBN到外侧下丘脑（LH）的投射介导味觉诱发的摄取的假设。我们将结合互补的解剖学、生理学和行为学技术来解决这一假设。我们提出以下具体目标：目的1：小鼠味觉PBN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励？这一假设将首先通过通道追踪和味觉诱发的fos样免疫反应（FLI）技术进行评估：我们将研究在完整或味觉盲的小鼠中，vta投射神经元是否优先被甜味、奖励刺激激活。我们还将使用体内记录技术从生理学上表征投射到VTA的味觉神经元。最后，我们将通过将该区域的损伤与行为分析相结合，来验证VTA对正常奖励功能至关重要，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从PBN到LH的直接投射介导味觉诱发摄入的假设，包括尿道追踪和味觉诱发的FLI，体内生理学和LH的损伤，随后测量行为。我们将在这些实验中使用味觉盲的trpm5缺失小鼠，以分离味觉和进食后反馈的影响。

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.