Synaptic Physiology of the Vestibular Periphery

前庭周围突触生理学

• 批准号: 10693357
• 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/10693357
• 关键词: 3-Dimensional; AMPA Receptors; Address; Anatomy; Area; Autonomic nervous system disorders; Bathing; Biological; Biophysical Process; Biophysics; Calculi; Cell Separation; Cells; Complex; Coupling; Crista ampullaris; Disease; Distal; Dizziness; Ear; Electric Stimulation; Electrodes; Elements; Environment; Epithelium; 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; Visualization; base; biophysical properties; cell type; cholinergic; experimental study; gamma-Aminobutyric Acid; imaging study; innovation; postsynaptic; presynaptic; 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由 它们上面的附属结构。这意味着毛细胞(HC)和初级传入细胞的进一步处理 电导，以及传入和传出突触。的并行模式使处理变得复杂 HCS和传入之间的传递，以及多个HC汇聚到单个传入。I型HCS 被传入的花萼包裹，在它们之间的裂隙中形成一个受限的体积。II型HCS突触 通过相对较小的接触区域到达花萼的外表面和/或到达圆盘末端。这将导致 三种类型的HC-到传入会聚。在最简单的形式中，HC仅在Bouton会聚到传入 结局。在花萼中发现了更多的复杂性，包括包围一个HC和 包含两个或更多个HC的复杂的花萼。最高的复杂性出现在二态结尾， 接受来自两种HC类型的输入，通过Bouton和内、外两面花瓣的组合 突触。先前的研究表明，对于花盏末端，快速的兴奋性量子传递通过 谷氨酸能AMPA受体可能受K+、H+和Ca~(2+)蓄积的调节。唇裂的动态变化 离子浓度的变化与HC或传入去极化有关。这些反过来又影响了两个国家的反应 I型HCS及其传入是由于面对裂隙的电导和平衡电位的变化。 其结果是，内面的帽状触点的性质与HC和传入的显著不同。 导体沐浴在散装的外淋巴中。因此，之前的单电极生物物理实验 Hcs或其在原位的传入，或在分离的细胞上，一直无法区分Hcs和 由突触间隙的独特体积所产生的相互作用所产生的传入 二。在本项目中，将对HC和传入突触进行生物物理和形态学实验 红耳龟后半规管壶腹脊成对取食 利用我们独特的能力，可以同时从HC和它联系的传入进行记录。这 方法将被用来表征突触间隙的离子环境，生物物理性质 HC和传入电导在HC及其相关的膜电位 传入是同时控制的，负责这些属性的结构元素。该项目 有两个主要目标：(1)对比从I型HCS到Hcs的突触输入的生物物理学和形态 花萼的内面，从II型Hcs到花萼外表面和/或花瓣端部 并检查离子和潜在传递体的累积对它们的调制；以及(2) 确定尼古丁和毒扁豆碱的作用机制、调节剂、作用部位和地区差异 胆碱能传出传入I型和II型肥厚型Hcs和隔着眉骨的肾盏传入。总体而言，该项目将提供 外周前庭信号处理的综合结构、功能生物物理特征。