Synaptic Physiology of the Vestibular Periphery

前庭周围突触生理学

• 批准号: 10488245
• 负责人: JONATHAN JAMES ART
• 金额: $ 65.38万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10488245
• 关键词: 3-Dimensional; AMPA Receptors; Address; Anatomy; Area; Autonomic nervous system disorders; Biological; Biophysical Process; Biophysics; Calculi; Cells; Complex; Coupling; Crista ampullaris; Disease; Distal; Dizziness; Electric Stimulation; Electrodes; Elements; Environment; Epithelial; Equilibrium; Face; Fiber; Functional disorder; Future; Glutamates; Goals; Hair Cells; In Situ; Ions; Kinetics; Labyrinth; Lateral; Mechanical Stimulation; Medial; Mediating; Membrane Potentials; Morphology; Muscarinics; Organ; Perilymph; Peripheral; Phase; Physiology; Positioning Attribute; Property; Receptor Cell; Reporting; Research; Role; Route; Sensory Hair; Site; Structure; Structure of posterior semicircular canal; Synapses; Synaptic Cleft; Synaptic Transmission; System; Testing; Turtles; Type I Hair Cell; Type II Hair Cell; Variant; Vertigo; base; biophysical properties; cell envelope; cell type; cholinergic; experimental study; gamma-Aminobutyric Acid; imaging study; innovation; postsynaptic; presynaptic; quantum; regional difference; response; signal processing; transmission process

Project Summary. Vestibular afferent responses deviate from the coherent mechanical stimulation imparted by their overlying accessory structures. This implicates further processing by hair cells (HCs) and primary afferent conductances, and by afferent and efferent synapses. Processing is complicated by the parallel modes of transmission between HCs and afferents, and the convergence of multiple HCs onto single afferents. Type I HCs are enveloped by an afferent calyx, creating a restricted volume in the cleft between them. Type II HCs synapse onto the external face of a calyx and/or onto bouton endings via relatively small contact areas. This results in three types of HC-to-afferent convergence. In the simplest form, HCs converge onto an afferent solely at bouton endings. Increased complexity is found at calyces, including both simple calyces enveloping one HC and complex calyces encompassing two or more HCs. The highest complexity occurs at dimorphic endings that receive input from both HC types through a combination of bouton and both inner- and outer-face calyceal synapses. Prior studies have shown that for calyceal endings, rapid excitatory quantal transmission via glutamatergic AMPA receptors may be modulated by K+, H+, and Ca2+ accumulation. Dynamic changes in cleft ion concentrations occur in response to HC or afferent depolarization. These in turn impact responses in both the type I HCs and their afferents due to changes in the conductances and equilibrium potentials facing the cleft. As a result, properties of inner-face calyceal contacts differ significantly from those of HC and afferent conductances bathed in the bulk perilymph. For that reason, prior single-electrode biophysical experiments on HCs or their afferents in situ, or on isolated cells, have been unable to distinguish the contributions of HCs and afferents resulting from reciprocal interactions created by the unique volume of the synaptic cleft coupling the two. In this project, biophysical and morphological experiments will be performed on HC and afferent synaptic pairs in the posterior semicircular canal crista ampullaris of the red-eared turtle, T. scripta elegans, taking advantage of our unique ability to record simultaneously from both a HC and the afferent it contacts. This approach will be used to characterize the ionic environment of the synaptic cleft, the biophysical properties of HC and afferent conductances under conditions where the membrane potentials of a HC and its associated afferent are controlled simultaneously, and the structural elements responsible for these properties. The project has two major aims: (1) to contrast the biophysics and morphology of synaptic inputs from type I HCs onto the internal face of the calyx with those from type II HCs onto the calyceal external face and/or bouton endings of nearby branches, and examine their modulation by accumulation of ions and potential transmitters; and (2) to identify the mechanisms, modulators, sites of action and regional differences in nicotinic and muscarinic cholinergic efferent input to type I and II HCs and calyx afferents across the crista. Overall, this project will provide an integrated structural, functional biophysical characterization of peripheral vestibular signal processing.

项目摘要。前庭传入反应偏离了相干机械刺激所给予的 它们上面的附属结构这意味着毛细胞（HC）和初级传入神经的进一步加工 传导，以及传入和传出突触。处理是复杂的并行模式 HC和传入之间的传输，以及多个HC向单个传入的会聚。第一类碳氢化合物 被传入花萼包围，在它们之间的裂缝中产生有限的体积。II型毛细胞突触 通过相对小的接触面积附着到花萼的外表面上和/或附着到终扣末端上。这导致 三种类型的HC-传入会聚。在最简单的形式中，HC仅在终扣处会聚到传入纤维上 结局增加的复杂性被发现在花萼，包括两个简单的花萼包围一个HC， 包含两个或多个毛细胞的复杂的花萼。最高的复杂性发生在二态性的末端， 通过终扣和内外面肾盏的组合接收来自两种HC类型的输入 突触先前的研究已经表明，对于肾盏末梢，快速兴奋性量子传输通过 钾离子、H+和Ca ~（2+）的积累可调节谷氨酸能AMPA受体。裂隙动态变化 离子浓度响应于HC或传入去极化而发生。这反过来又影响了两个方面的反应， I型HC和它们的传入由于面对裂缝的电导和平衡电位的变化。 因此，内面肾盏接触的性质与HC和传入纤维的性质显著不同 沐浴在大量外淋巴液中的电导。由于这个原因，先前的单电极生物物理实验 毛细胞或它们的传入神经在原位或在分离的细胞上，已经不能区分毛细胞的贡献， 由突触间隙的独特体积所产生的相互作用产生的传入神经耦合， 两个.本课题将对HC和传入突触进行生物物理学和形态学实验， 在后半规管壶腹嵴中有2对，在后半规管壶腹嵴中有2对，在后半规管壶腹嵴中有2对，在后半规管壶腹嵴中有2对。优雅的手稿， 我们的独特能力，同时记录从HC和传入它接触的优势。这 方法将被用来表征突触间隙的离子环境，生物物理特性， HC和传入电导的条件下，HC的膜电位及其相关的 同时控制传入，和负责这些属性的结构元素。项目 有两个主要目的：（1）将来自I型HC的突触输入的生物物理学和形态学与来自I型HC的突触输入的生物物理学和形态学进行对比。 与来自II型毛细胞的毛萼内表面的毛萼外表面和/或 附近的分支，并检查其调制的离子和潜在的发射器的积累;和（2）， 确定烟碱和毒蕈碱的机制、调节剂、作用位点和区域差异 胆碱能传出输入到I型和II型HC和跨嵴的花萼传入。总的来说，该项目将提供 外周前庭信号处理的综合结构、功能生物物理表征。