Auditory Coding at the Hair Cell Ribbon Synapse

毛细胞带突触的听觉编码

• 批准号: 8390788
• 负责人: Geng-Lin Li
• 金额: $ 24.92万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-02 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8390788
• 关键词: Acoustic Nerve; Amphibia; Auditory; Calcium; Cells; Cochlea; Cochlear Implants; Code; Dependence; Dyes; Electric Capacitance; Electrodes; Endocytosis; Fiber; Hair Cells; Hearing; Image; Implant; Instruction; Knowledge; Measurement; Measures; Membrane; Membrane Potentials; Microscope; Microscopy; Monitor; Nerve Fibers; Patients; Phase; Photons; Rana catesbeiana; Recycling; Resolution; Signal Transduction; Simulate; Site; Synapses; Synaptic Transmission; Synaptic Vesicles; Time; Ultraviolet Rays; United States; Variant; Vesicle; analog; digital; feeding; flash photolysis; in vivo; postsynaptic; presynaptic; response; ribbon synapse; sound; tongue papilla; two-photon; voltage

Hair cells in the cochlea connect to auditory afferent fibers via ribbon synapses, which convert presynaptic gracied potentials (analog signal) Into postsynaptic all-or-none spikes (digital signal). The long-term objective of this study is to investigate mechanisms of synaptic transmission and strategies for auditory coding at these synapses. Previously, by determining the quantal size of the hair cell ribbon synapse in bullfrog j amphibian papilla, we demonstrated unequivocally that hair cells can release more than one synaptic vesicle at a time (multivesicular release, MRV) from a single release site (i.e., ribbon). To study cellular mechanisms that control MRV, we will measure the calcium-dependence of MVR and determine its calcium threshold. To demonstrate the functional advantages of MRV, we will first stimulate hair cells with sinusoidal presynaptic depolarizations that mimic hair cell voltage responses in vivo, and quantify MVRs in the evoked EPSCs. Then we simulate two sets of EPSCs in which we either substitute MVRs with evenly distributed single vesicle releases within a time window (e.g., 0.1 ms), or fix the quantal content of MVRs (removing the variation in their quantal contents). We will feed both the original and simulated EPSCs to afferent fibers under current-clamp, and find out to what extent the phase-locking of spikes gets deteriorated. To investigate how synaptic vesicles are recycled, we will use a two-photon microscope to visualize FM1-43 dye loading to monitor vesicle recycling, and we will also make cell-attached capacitance measurement on hair cells to study vesicle recycling by monitoring capacitance changes with a submillisecond time resolution.

耳蜗中的毛细胞通过色带突触连接到听觉传入纤维，这些传入纤维转化为突触前 在突触后全或无尖峰（数字信号）中进行葡萄质电位（模拟信号）。长期目标 这项研究的是研究突触传播的机制和在 这些突触。以前，通过确定Bullfrog J中毛细胞色带突触的量化量 两栖动物乳头，我们明确地证明了毛细胞可以释放多个突触囊泡 一次（从单个释放位点（即功能区），一次（多重释放，MRV）。研究细胞机制 控制MRV，我们将测量MVR的钙依赖性并确定其钙阈值。到 证明MRV的功能优势，我们将首先用正弦突触刺激毛细胞 去极化，模拟体内模拟毛细胞电压反应，并在诱发的EPSC中量化MVR。 然后，我们模拟了两组EPSC，其中我们用均匀分布的单个替换MVR 囊泡在时间窗口内释放（例如0.1 ms），或修复MVR的定量含量（删除 其数量内容的变化）。我们将将原始EPSC和模拟的EPSC喂给传入纤维 在电流夹下，并找出尖峰的相锁定在多大程度上恶化。调查 突触囊泡的回收方式如何，我们将使用两光子显微镜可视化FM1-43染料加载到 监视囊泡回收，我们还将在毛细胞上进行细胞跟踪的电容测量 通过亚微分辨率分辨率来监测电容的变化来研究囊泡回收。