Cellular Mechanisms of the Vestibular System

超出提供的空间。我们将研究传入和传出突触的机制，长期目标是了解I型和II型毛细胞以及传出控制对前庭功能的独特贡献。工作是在海龟的后脊和椭圆形黄斑上完成的。有两个具体的目的：1)通过记录传入终末和毛细胞来研究传入突触的传递。传递既包括量子机制，也包括非量子机制，在数量上，后者在花萼着生纤维中比在花冠纤维中更重要。我们将确定含花萼纤维中的量子活动是否起源于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。将从突触后NMDA和非NMDA受体的参与、脱敏、谷氨酸转运体、突触前谷氨酸受体以及从传入到毛细胞的逆行传递等方面比较这两种纤维的量子活性。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)研究电刺激传出纤维引起的突触活动。Bouton单位的传出反应取决于它们在脊神经上皮细胞中的位置，范围从平面附近的弱兴奋到环面附近的强抑制。花萼单位表现出强烈的兴奋性，包括快反应和慢反应。我们建议继续研究每一类传入的突触和受体机制。我们将研究毛细胞传出突触的共同特征--突触下池是否起到钙储存的作用，从而改变传出动作，并确定不同传入细胞对感觉输入的反应是如何被传出激活所改变的。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了解人类前庭功能至关重要，因为在人类中，这些毛细胞的数量超过了II型毛细胞，更容易受到病原体的影响。该提案利用海龟来研究在哺乳动物中很难(如果不是不可能)研究的问题。一个优点是可以在单个器官中研究各种传出动作。表演网站========================================Section End===========================================

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===========================================