Efferent Innervation of Identified Vestibular Afferents

描述（由申请人提供）：本基金的目的是研究外周前庭器官的传出神经支配。对脑干传出神经元到外周迷路的神经递质和投射的了解将有助于我们理解该系统在健康和疾病中的作用。我们建立在我们过去的工作表明，前庭传出神经元是异质性的递质组成和外周目标。这种异质性挑战了我们长期以来的观点，即前庭传出神经是一个非特异性系统。实验是在灰鼠身上进行的，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，用于研究传出系统的结构组织与共聚焦和电子显微镜。通过顺行示踪剂注射到它们的脑干起源核和它们在外周的独特的突触分布来识别外周的传出神经元。传入类别通过特异性免疫组织化学标记物（钙视网膜蛋白、外周蛋白）来鉴定。传出结构与毛细胞和传入类，并与嵴和黄斑的区域组织。具体目标是：1）通过顺行追踪确定脊和黄斑中同侧、对侧和双侧投射传出神经元的投射模式和终末野; 2）确定烟碱。毛细胞和传入纤维上的毒蕈碱和CGRP受体亚型;和3）检查传出作用的亚细胞机制，特别是突触下脑池中钙相关泵和通道的定位。其目的是产生一个身体的形态学，神经化学和细胞生物学知识，从生理学和可验证的假说可以得出。

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.