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 它们上覆的配件结构。这意味着毛细胞（HCS）和主要传入的进一步处理 电导，以及传入和传出的突触。处理的平行模式使处理变得复杂 HCS和传入之间的传播，以及多个HC的收敛到单个传入。类型I HCS 被传入的花萼包裹，在它们之间的裂缝中造成了限制的体积。 II型HCS突触 通过相对较小的接触区域进入花萼的外表面和/或到胸部末端。这导致 三种类型的HC到代价收敛。以最简单的形式，HCS仅在Bouton上收敛到一个传入 结局。在钙式下发现复杂性的提高，包括包裹一个HC和 复杂的钙包含两个或多个HC。最高复杂性发生在二态结尾处 通过Bouton和内部和外面的Calyceal从两种类型的HC类型中接收输入 突触。先前的研究表明，对于钙化结尾，通过 谷氨酸能AMPA受体可以通过K+，H+和Ca2+积累来调节。裂缝的动态变化 离子浓度响应于HC或传入的去极化。这些反过来影响两者的反应 I型HCS及其传入是由于电导率和裂缝面向脉冲的平衡电位的变化而引起的。 结果，内面钙化接触的性能与HC和传入的特性显着不同 电导在散装的围绕围绕中。因此，先前的单电极生物物理实验 HCS或其传入原地或孤立的细胞无法区分HCS和 由突触裂缝的唯一体积耦合产生的相互作用产生的传入 二。在这个项目中，将在HC和传入突触中进行生物物理和形态学实验 在后半圆形的crista ampullaris中，红耳乌龟T. Scripta Elegrans的对成对 我们独特的能力可以从HC和IT接触的传入中同时记录。这 方法将用于表征突触裂缝的离子环境，即 HC和传入电导在HC及其相关的膜电位的条件下 同时控制传入，以及负责这些特性的结构元素。项目 有两个主要目的：（1）将I型HCS的突触输入的生物物理学和形态进行对比 花萼的内部面，其中II型HC的脸部到花序的外部面和/或BOUTON的末端 附近的分支，并通过离子和潜在发射器的积累来检查它们的调节； （2）到 确定烟碱和毒蕈碱的机制，调节器，作用部位以及区域差异 Crista的I型和II型HC和花萼传入的胆碱能传递输入。总体而言，该项目将提供 周围前庭信号处理的综合结构，功能性生物物理表征。