Cellular Mechanisms of the Vestibular System

前庭系统的细胞机制

• 批准号: 6582013
• 负责人: JAY M GOLDBERG
• 金额: $ 57.57万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6582013
• 关键词: Chelonia; NMDA receptors; action potentials; afferent nerve; behavioral /social science research tag; cell population study; ear hair cell; efferent nerve; glutamate transporter; membrane potentials; morphometry; neural transmission; neuron component; neuronal transport; neurotransmitter receptor; nicotinic receptors; receptor sensitivity; sensory signal detection; synapses; vestibular pathway

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.

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。工作是在龟后嵴和椭圆囊黄斑中完成的。具体目标有两个： 1）通过传入神经末梢和毛细胞的记录来研究传入突触传递。传输涉及量子和非量子机制，后者在数量上在花萼轴承中比在布顿纤维中更重要。我们将确定萼纤维中的量子活动是否起源于 I 型毛细胞。将评估非量子传输的机制及其在前庭转导中的作用。两种纤维的量子活性将在突触后 NMDA 和非 NMDA 受体的参与、脱敏、谷氨酸转运蛋白、突触前谷氨酸受体以及从传入到毛细胞的逆行传递方面进行比较。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) 研究传出纤维电激活引起的突触活动。布顿单元的传出反应取决于它们在嵴中的神经上皮位置，范围从平面附近的弱激发到环面附近的强抑制。花萼单元显示出强烈的激发，包括快速和慢速响应。我们建议继续研究几类传入神经的突触和受体机制。我们将检查突触下池（毛细胞传出突触的一个共同特征）是否充当可以修改传出动作的 Ca 2+ 存储，并确定如何通过传出激活来修改对各种传入神经中感觉输入的反应。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于了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。该提案利用海龟来研究在哺乳动物中研究起来困难甚至不可能的问题。一个优点是可以在单个器官中研究多种传出动作。