Cellular Mechanisms of the Vestibular System

描述（由申请人提供）：我们将研究传入和传出突触机制，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。工作是在海龟后嵴和椭圆囊黄斑。有两个具体目标： 1)从传入终末和毛细胞记录研究传入突触传递。传输涉及量子和非量子机制，后者在数量上更重要的是在花萼轴承，比在扣，纤维。我们将确定是否量子活动在花萼轴承纤维起源于I型毛细胞。非量子传输的机制及其在前庭传导中的作用将被评估。在两种纤维的量子活动将比较突触后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，从传入到毛细胞的逆行传递。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蛋白的身份和分布。 2)研究电刺激传出纤维诱发的突触活动。输出反应的bouton单位取决于它们的神经上皮细胞的位置在嵴，范围从弱的兴奋附近的平面到强抑制附近的环面。花萼轴承单位表现出强烈的兴奋，包括快速和缓慢的反应。我们建议继续研究的突触和受体机制的几类传入。我们将研究是否突触下池，毛细胞传出突触的一个共同特征，作为一个Ca 2+存储，可以修改传出动作，并确定如何在各种传入的感觉输入的反应被修改传出激活。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的数量超过II型毛细胞，并且更容易受到病理因素的影响。这项提议利用海龟来研究哺乳动物中很难（如果不是不可能的话）研究的问题。一个优点是可以在单个器官中研究传出动作的多样性。

DESCRIPTION (provided by applicant): 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. Transmission 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 originates 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 postsynaptic NMDA and non-NMDA receptors, desensitization, glutamate transporters, presynaptic glutamate receptors, and retrograde transmission from afferents to hair cells. Morphological studies will clarify the distribution and number of ribbon synapses, as well as the identity and distribution of glutamate receptors and transporters. 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.