Cellular Mechanisms of the Vestibular System

超出所提供的空间。我们将研究传入和传出突触机制，以了解I型和II型毛细胞以及传出控制对前庭功能的独特贡献。在海龟后嵴和室斑处进行手术。有两个具体的目的：1)通过记录传入末端和毛细胞来研究传入突触的传递。传输涉及量子和非量子机制，后者在花萼中比在钮扣纤维中更重要。我们将确定花萼纤维的量子活性是否起源于I型毛细胞。非量子传递的机制及其在前庭传导中的作用将被评估。我们将从突触后NMDA和非NMDA受体的参与、脱敏、谷氨酸转运体、突触前谷氨酸受体的参与以及从传入到毛细胞的逆行传递等方面比较两种纤维的量活性。形态学研究将阐明带状突触的分布和数量，以及谷氨酸受体和转运体的身份和分布。2)研究电激活传出纤维所引起的突触活动。钮扣单元的传出反应取决于其在嵴中的神经上皮位置，范围从平面附近的弱兴奋到环面附近的强抑制。花萼单元表现出强烈的激励，包括快速和慢速响应。我们建议继续研究这几类传入事件的突触和受体机制。我们将研究亚突触池（毛细胞传出突触的共同特征）是否作为ca2 +储存库，可以修改传出动作，并确定对各种传入的感觉输入的反应如何通过传出激活来修改。形态学研究将阐明传出突触的分布和数量，以及烟碱和其他传出相关受体的身份和分布。发现I型毛细胞的独特贡献可能对理解人类前庭功能至关重要，因为这些毛细胞在人类中数量超过II型毛细胞，并且更容易受到病理因子的影响。该提案利用海龟来研究在哺乳动物身上很难研究的问题，如果不是不可能的话。一个优点是可以在单个器官中研究多种传出动作。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. We will study both afferent and efferent synaptic mechanisms with the long-term objective of understanding the distinctive contributions made by type I and type II hair cells and by efferent control to vestibular function. Work is done in the turtle posterior crista and utricular macula. There are two specific aims: 1) To study afferent synaptic transmission by recording from afferent terminals and hair cells. Transmis- sion involves both quantal and non-quantal mechanisms with the latter being quantitatively more important in calyx-bearing, than in bouton, fibers. We will determine whether quantal activity in calyx-bearing fibers origi- nates in type I hair cells. The mechanisms of non-quantal transmission and its role in vestibular transduction will be assessed. Quantal activity in the two kinds of fibers will be compared in terms of the participation of postsynaptie NMDA and non-NMDA receptors, desensitization, glutamate transporters, presynaptic glutamate receptors, and retrograde transmission from afferents to hair cells. Morphological studies will clarify the distri- bution and number of ribbon synapses, as well as the identity and distribution of glutamate receptors and trans- porters. 2) To study the synaptic activity evoked by electrical activation of efferent fibers. Efferent responses of bouton units depend on their neuroepithelial location in the crista, ranging from weak excitation near the planum to strong inhibition near the torus. Calyx-bearing units show a strong excitation, consisting of both fast and slow responses. We propose to continue studies of synaptic and receptor mechanisms for each of the several classes of afferents. We will examine whether the subsynaptic cistern, a common feature of hair-cell efferent synapses, acts as a Ca 2+store that can modify efferent actions and determine how responses to sensory inputs in various afferents are modified by efferent activation. Morphological studies will clarify the distribution and numbers of efferent synapses, as well as the identity and distribution of nicotinic and other efferent-related receptors. Finding the distinctive contribution of type I hair cells may be critical to understanding human vestibular function as these hair cells outnumber type II hair cells in man and are more vulnerable to pathological agents. The proposal takes advantage of the turtle to study problems that would be difficult, if not impossible, to study in mammals. One advantage is the variety of efferent actions that can be studied in a single organ. PERFORMANCE SITE ========================================Section End===========================================