Efferent Innervation of Identified Vestibular Afferents

描述（由申请人提供）：本资助的目的是研究外周前庭器官的传出神经支配。了解神经递质和从脑干传出神经元到外周迷宫的投射将有助于我们理解该系统在健康和疾病中的作用。我们建立在我们过去的工作表明，前庭传出神经元是异质的，在他们的递质组成和外周目标。这种异质性挑战了我们长期持有的前庭传出是一个非特异性系统的观点。实验是在栗鼠身上进行的，将集中在传出系统的外围组织上。解剖，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。外周的传出神经元是通过对其脑干起源核的顺行示踪剂注射和它们在外周的独特突触谱来识别的。传入类通过特定的免疫组织化学标记物（calretinin, peripherin）来识别。传出结构与毛细胞和传入类有关，与嵴和黄斑的区域组织有关。具体目的是：1)通过顺行追踪确定嵴和黄斑中同侧、对侧和双侧投射的传入神经元的投射模式和终端场；2)指定尼古丁。3)研究传出作用的亚细胞机制，特别是突触亚池中钙相关泵和通道的定位。其目的是产生一个形态学、神经化学和细胞生物学知识体系，从中可以推导出生理学和药理学上可检验的假设。

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.