Efferent Innervation of Identified Vestibular Afferents

描述(申请人提供)：这项资助的目的是调查外周前庭装置的传出神经支配。了解从脑干传出神经元到外周迷路的神经递质和投射将有助于我们理解该系统在健康和疾病中的作用。我们在过去工作的基础上提出前庭传出神经元在它们的递质组成和外周靶点上是不同的。这种异质性挑战了我们长期以来认为前庭传出是一个非特异性系统的观点。实验在栗鼠身上进行，将集中在传出系统的外围组织上。解剖学，以及免疫组织化学和其他分子方法，被用来研究传出系统的结构组织与共聚焦和电子显微镜。外周的传出神经元通过顺行示踪剂注入起源于它们的脑干核团和它们在外周的独特的突触轮廓来识别。通过特定的免疫组织化学标记物(钙维A、外周蛋白)识别传入类别。传出结构与毛细胞和传入分类有关，与眉骨和斑点的区域组织有关。具体目标是：1)通过顺行追踪同侧、对侧和双侧在眉骨和斑点投射的传出神经元的投射模式和终末野；2)确定烟碱。毛细胞和传入细胞上的M受体和CGRP受体亚型：3)研究传出作用的亚细胞机制，特别是突触下池中与钙相关的泵和通道的定位。其目的是产生一套形态、神经化学和细胞生物学知识，从中可以得出生理学和药理学上可测试的假说。

DESCRIPTION (provided by applicant): The purpose of this grant is to investigate the efferent innervation of the peripheral vestibular apparatus. Knowledge of the neurotransmitters and projections from brainstem efferent neurons to the peripheral labyrinth will help us to understand the role of this system in health and disease. We build on our past work suggesting that vestibular efferent neurons are heterogeneous in their transmitter composition and peripheral targets. Such heterogeneity challenges our long-held view that vestibular efferents are a nonspecific system. Experiments are done in the chinchilla and will concentrate on the peripheral organization of the efferent system. Anatomical, as well as immunohistochemical and other molecular approaches, are used to study the structural organization of the efferent system with both confocal and electron microscopy. Efferent neurons in the periphery are identified by means of anterograde tracer injections into their brainstem nuclei of origin and their distinctive synaptic profiles in the periphery. Afferent classes are identified by means of specific immunohistochemical markers (calretinin, peripherin). Efferent structure is correlated with hair cell and afferent classes and with the regional organization of the cristae and maculae. Specific aims are: 1) to determine by anterograde tracing the projection patterns and terminal fields of ipsilaterally-, contralaterally-, and bilaterally-projecting efferent neurons in the cristae and maculae: 2) to specify nicotinic. muscarinic and CGRP receptor subtypes on hair cells and afferents: and 3) to examine subcellular mechanisms of efferent action, specifically the localization of calcium-related pumps and channels in subsynaptic cisterns. The intent is to produce a body of morphological, neurochemical and cell biological knowledge from which physiologically and pharmacologically testable hypotheses can be derived.