Synaptic Physiology of the Vestibular Periphery

前庭周围突触生理学

• 批准号: 10342422
• 负责人: JONATHAN JAMES ART
• 金额: $ 67.87万
• 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/10342422
• 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.

项目总结。前庭传入反应偏离连贯机械刺激的传递