Synaptic specialization of auditory hair cells

翻译后摘要：外周听觉系统与中枢神经系统的沟通，通过 感觉细胞和螺旋神经节神经元之间的突触。这个突触携带着 关于频率、强度和时间的信息，CNS用于提取所有 由听觉模态提供的信息。突触是专门在一个广泛的 频率范围，以线性方式响应分级刺激。突触保持高速率 不疲劳，对受体电位敏感，通常低于1 mV。的目标 这个建议是为了描述这些不寻常的突触特性的机制。术前 和突触后机制进行研究。具体目标1解决突触前问题， 有三个子目标：识别囊泡释放和运输的Ca 2+依赖成分， 确定释放动力学，同时确定运输和释放的限速步骤，和 阐明释放特性的张力分布差异，表征Ca 2+稳态机制 其调节释放并鉴定释放和运输的磷酸化依赖性调节。 具体目标2研究突触后处理有三个目标;首先确定是否有 可能有助于增强频率选择性的传入电特性的音调分布变化 例如电压依赖性过程的动力学和幅度，其次是表征突触 在不同的位置传播，以确定受体类型和数量的差异，第三， 研究与多泡释放相关的机制。结构，免疫细胞化学， 光学、电生理和理论工具，包括几种新技术， 使我们能够更好地调查这些问题。考虑到大脑皮层突触传递的任何缺陷 毛细胞传入纤维突触导致听觉缺陷，确定新的机制可能提供 独特的干预途径。

Abstract: The peripheral auditory system communicates with the central nervous system through synapses between the sensory cells and the spiral ganglion neurons. This single synapse carries information regarding frequency, intensity and timing that is used by the CNS for to extract all information provided by the auditory modality. The synapse is specialized to operate across a broad frequency range, to respond to graded stimuli in a linear manner. The synapse maintains high rates of release and does not fatigue and is sensitive to receptor potentials often below 1 mV. The goal of this proposal is to delineate the mechanisms underlying these unusual synaptic properties. Both pre and postsynaptic mechanisms will be investigated. Specific Aim 1 addresses presynaptic issues and has three subaims; to identify the Ca2+ dependent components of vesicle release and trafficking, to determine the kinetics of release while identifying the rate limiting steps of trafficking and release, and to elucidate tonotopic differences in release properties, characterizing Ca2+ homeostatic mechanisms that regulate release and identifying phosphorylation dependent regulation of release and trafficking. Specific Aim 2 investigates postsynaptic processing with three goals; first to determine if there are tonotopic variations in afferent electrical properties that might serve to enhance frequency selectivity such as the kinetics and magnitude of voltage-dependent processes, second to characterize synaptic transmission at different locations to identify differences in receptor types and numbers and third to investigate mechanisms associated with multivesicular release. Structural, immunocytochemical, optical, electrophysiological and theoretical tools including several new technologies are included to better enable us to investigate these issues. Given that any deficits in synaptic transmission at the hair cell afferent fiber synapse results in auditory deficits, identifying novel mechanisms may provide unique avenues for intervention.