Neural Plasticity in the Adult Gustatory System

描述（由申请人提供）：味蕾对神经支配的依赖性已被用作理解神经/靶标相互作用的模型。神经支配的丧失导致味蕾正常形态外观的丧失，而神经支配的恢复导致味蕾形态和功能的恢复。成人再生的味觉系统特别容易受到环境操纵的影响。除了与鼓室索神经外周部分相关的损伤引起的影响外，也有极端的形态学变化涉及到被切片的神经的中心部分。总的来说，这些发现表明，成年人的外周和中枢味觉系统在成年期具有特别的可塑性。协调的研究将集中在损伤诱导的味觉神经元在其周围和中枢目标的可塑性。为了开始研究这些事件背后的潜在机制，拟议研究的一个重点是研究脑源性神经营养因子（BDNF）在维持成年期味觉神经元形态和功能特征方面的作用，以及在切除鼓室索神经（CTX）时伴随的退行性/再生过程中的作用。将解剖学、神经生理学、分子遗传学和细胞/分子技术结合起来，使用维持单侧CTX的大鼠和小鼠进行实验，将使我们能够：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，确定CTX诱导的NST功能可塑性；2)确定成年期从舌上皮中去除BDNF后，周围和中枢味觉系统的维持是如何改变的，以及这种去除如何影响ctx诱导的系统变性和再生。3)确定成年期从大多数组织（包括舌上皮、膝状神经节和NST）中去除BDNF后，周围和中枢味觉系统的维持和ctx诱导的变性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：感觉编码，神经活动在维持感觉功能中的作用，以及正常情况下和神经损伤反应下外周神经支配的时间稳定性和准确性。结果也将使更清楚地了解人类味觉神经损伤的神经生物学后遗症病理持续，或在中耳或口腔手术。

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.