Synaptic specialization of auditory hair cells

摘要：外周听觉系统与中枢神经系统通过 感觉细胞和螺旋神经节神经元之间的突触。这个单一的突触携带着 关于CNS使用的频率、强度和定时的信息，用于提取所有 由听觉通道提供的信息。突触是专门用来在广泛的 频率范围，以线性方式对分级刺激作出反应。突触维持较高的速率 释放速度快，不会疲劳，对受体电位通常低于1 mV很敏感。的目标是 这项提议是为了描述这些不寻常的突触特性背后的机制。两个版本都在 并将研究突触后机制。具体目标1解决突触前问题和 有三个子目标；确定囊泡释放和运输的依赖于钙的成分， 确定释放的动力学，同时确定贩运和释放的速率限制步骤，以及 阐明张力释放特性的差异，表征钙离子的稳态机制 调节释放和识别依赖于磷酸化的释放和运输的调节。 具体目标2研究突触后的处理有三个目标；第一个目标是确定 可能有助于提高频率选择性的传入电特性的音调变化 例如电压依赖过程的动力学和大小，其次是突触的特征 在不同位置的传播，以识别受体类型和数量的差异，第三到 研究与多囊释放相关的机制。结构，免疫细胞化学， 包括光学、电生理和理论工具，包括几项新技术 更好地使我们能够调查这些问题。鉴于在突触传递方面的任何缺陷 毛细胞传入纤维突触导致听力障碍，识别新的机制可能提供 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.