Neural Plasticity in the Adult Gustatory System

描述(申请人提供)：味蕾对神经支配的依赖已被用作理解神经/目标相互作用的模型。失去神经支配会导致味蕾失去正常的形态外观，而神经支配的恢复会导致味蕾形态和功能的恢复。成人的味觉再生系统特别容易受到环境操纵的影响。除了与鼓索神经的外周部分相关的损伤诱导的影响外，还存在涉及切断的神经的中央部分的极端形态变化。总而言之，这些发现表明，成人的外周和中央味觉系统在成年时尤其具有可塑性。协调研究将集中在损伤诱导的味觉神经元在其外周和中央靶点的可塑性。为了开始探讨这些事件可能的候选机制，拟议的研究的一个关键焦点是检查脑源性神经营养因子(BDNF)在成年时维持味觉神经元的形态和功能特征方面的作用，以及伴随着切断鼓索神经(CTX)而发生的退化/再生过程。结合解剖学、神经生理学、分子遗传学和细胞/分子技术，在大鼠和小鼠接受单侧CTX的实验中，我们将能够：1)通过记录中枢味觉反应，同时刺激个体不同的味觉受体群体，来确定CTX诱导的NST的功能可塑性；2)确定成年期从舌上皮细胞中去除BDNF时，周围和中央味觉系统的维持是如何改变的，以及这种去除如何影响环磷酰胺诱导的系统退化和再生；以及3)确定成年期从包括舌上皮、膝状神经节和NST在内的大多数组织中去除BDNF时，周围和中央味觉系统的维持和由CTX诱导的退化和再生是如何受到影响的。这些研究的结果将涉及更广泛的主题，包括感觉编码，神经活动在维持感觉功能中的作用，以及在正常情况下和在应对神经损伤时周围神经支配的时间稳定性和准确性。研究结果还将使人们更清楚地了解人类味觉神经损伤的神经生物学后遗症，这些后遗症是在病理上或在中耳或口腔手术期间遭受的。 公共卫生相关性： 项目简介：味觉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。因此，味觉系统在人类健康中扮演着重要的角色。这项研究的目的是研究在动物模型中切断味觉神经后味觉系统的结构和功能是如何改变的，并反映出人类在病理、中耳手术或口腔手术中的后果。

DESCRIPTION (provided by applicant): The dependence of taste buds on innervation has been used as a model to understand nerve/target interactions. Loss of innervation results in a loss of the normal morphological appearance of taste buds, while restoration of innervation results in a recovery of taste bud morphology and function. The adult regenerating gustatory system is especially susceptible to environmental manipulations. In addition to injury-induced effects related to the peripheral portion of the chorda tympani nerve, there are also extreme morphological changes that involve the central portion of the sectioned nerve. Collectively, these findings show that the adult peripheral and central gustatory system is especially plastic at adulthood. Coordinated studies will focus on the injury-induced plasticity in gustatory neurons at their peripheral and central targets. To begin addressing candidate mechanisms that may underlie these events, a key focus of proposed studies is to examine the role of Brain Derived Neurotrophic Factor (BDNF) on maintaining the morphological and functional characteristics of gustatory neurons at adulthood, and on degenerative/regenerative processes that are attendant to sectioning the chorda tympani nerve (CTX). Combined anatomical, neurophysiological, molecular genetic, and cellular/molecular techniques in experiments using rats and mice sustaining unilateral CTX will permit us to: 1) determine the CTX-induced functional plasticity in the NST by recording central taste responses while stimulating individual, distinct taste receptor populations; 2) determine how maintenance of the peripheral and central gustatory system is altered when BDNF is removed from lingual epithelia at adulthood, and how this removal affects CTX-induced degeneration and regeneration of the system, and 3) determine how maintenance and CTX-induced degeneration and regeneration of the peripheral and central gustatory system is affected when BDNF is removed from most tissues at adulthood, including lingual epithelia, the geniculate ganglion, and the NST. Findings from these studies will address the broader topics of sensory coding, the role of neural activity in maintenance of sensory function, and the temporal stability and accuracy of peripheral innervation under normal circumstances and in response to nerve damage. Results will also enable a clearer understanding of the neurobiological sequelae of human taste nerve damage sustained pathologically, or during middle ear or oral surgery. PUBLIC HEALTH RELEVANCE: Project Narrative: The sense of taste plays a key role in a number of human conditions that include obesity, diabetes, anorexia, hypertension, and coronary artery disease. As such, the gustatory system plays an important role in human health. The goal of this research is to examine how the structure and function of the gustatory system is altered following cutting a taste nerve in animal models, and reflect consequences in humans attendant to pathology, middle ear surgery, or oral surgery.