Regulation of exo- and endocytosis at ribbon synapses of auditory hair cells

听觉毛细胞带状突触的外吞和内吞作用的调节

基本信息

批准号：
8834855
负责人：
Owen P Gross
金额：
$ 5.33万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-01-10 至 2016-01-09
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8834855
关键词：
ATP phosphohydrolase Acoustics Address Affect Afferent Neurons Agonist Amphibia Area Auditory Auditory Perception Biochemical Biological Assay Brain Buffers Cell surface Cells Code Complex Cytoplasm Data Dependence Docking Ear Electric Capacitance Endocytosis Ensure Environment Equilibrium Event Exhibits Exocytosis Fiber Frequencies Goals Hair Cells Hearing Individual Investigation Isradipine Lead Life Measurement Measures Membrane Membrane Potentials Methods Modeling Molecular Nervous system structure Neurons Neurotransmitters Output Pathway interactions Perception Phase Physiological Play Preparation Process Property Protocols documentation Protons Pump Rana catesbeiana Receptor Signaling Recycling Regulation of Exocytosis Research Rest Role Series Signal Transduction Solutions Stimulus Structure Synapses Synaptic Vesicles System Testing Time Vertebrates Vesicle Visual auditory discrimination base channel blockers computerized tools deafness design improved mathematical model neurotransmitter release operation patch clamp postsynaptic presynaptic programs protein complex public health relevance receptor relating to nervous system research study response ribbon synapse sensory system sound synaptic function tongue papilla transmission process vibration visual information voltage

项目摘要

DESCRIPTION (provided by applicant): Perception of the external world begins with transduction of physical stimuli into biochemical signals by receptor neurons. To propagate these signals throughout the nervous system, receptor neurons in both the auditory and visual information pathways of vertebrates employ specialized synapses characterized by a dense presynaptic structure known as a ribbon. Synaptic ribbons possess unique features thought to facilitate sustained, low-latency exocytosis of neurotransmitter in response to activation of the presynaptic transduction cascade. Disruption of ribbon synapse function in auditory hair cells, which detect acoustic vibrations, can cause deafness, demonstrating the central role of ribbons in auditory perception. More subtle observations of auditory ribbon synapses have revealed several puzzling properties that could influence functional encoding of auditory information. Specifically, measurements of neurotransmitter release from hair cells show simultaneous exocytosis of multiple vesicles, a phenomenon known as multivesicular release that represents a potential coding strategy for amplifying weak signals or for ensuring temporal precision of encoded auditory information. Additionally, in order to maintain a high rate of neurotransmitter release during sustained stimulation, the neurotransmitter vesicle pool must be continuously recycled, a process that involves endocytosis of previously fused vesicles. The mechanisms that regulate replenishment of the vesicle pool are poorly understood in hair cells, although observations from other neural systems provide clues about which intracellular signals might play regulatory roles in this process. Even less is known about the mechanisms that facilitate multivesicular release. These phenomena will be investigated using paired electrophysiological recordings from auditory hair cells and postsynaptic afferent fibers in the bullfrog (Rana catesbeiana) amphibian papilla. Experiments will be conducted using stimulation protocols and recording solutions specially designed to test the requirements for multivesicular release and the role of pH in controlling the rate of vesicle recycling. Computational tools will be developed for analyzing the instantaneous rate of exocytosis during complex evoked release events and for modeling presynaptic pH dynamics immediately following exocytosis. Results from these experiments have the potential to reveal molecular mechanisms and signaling strategies important not only to the process of auditory perception, but also to the general understanding of how sensory neurons encode and sustain information-rich signals describing a broad array of stimulus features.

描述（由申请人提供）：对外部世界的感知始于受体神经元将物理刺激转变成生化信号。为了在整个神经系统中传播这些信号，脊椎动物的听觉和视觉信息通路中的受体神经元都使用专门的突触，其特征是称为带状的致密突触前结构。突触带具有独特的特征，被认为可以促进神经递质响应突触前转导级联的激活而进行持续、低延迟的胞吐作用。听觉毛细胞中负责检测声音振动的带状突触功能的破坏可能导致耳聋，这表明了带状突触在听觉感知中的核心作用。对听觉带状突触的更微妙的观察揭示了一些令人费解的特性，这些特性可能会影响听觉信息的功能编码。具体来说，毛细胞神经递质释放的测量显示多个囊泡同时胞吐，这种现象称为多囊泡释放，代表了放大微弱信号或确保编码听觉信息的时间精度的潜在编码策略。此外，为了在持续刺激期间保持神经递质释放的高速率，神经递质囊泡池必须不断回收，这一过程涉及先前融合的囊泡的内吞作用。尽管其他神经系统的观察提供了关于哪些细胞内信号可能在此过程中发挥调节作用的线索，但对毛细胞中调节囊泡池补充的机制知之甚少。对于促进多囊泡释放的机制知之甚少。这些现象将使用来自牛蛙（Rana catesbeiana）两栖动物乳头的听觉毛细胞和突触后传入纤维的配对电生理记录进行研究。实验将使用专门设计的刺激方案和记录溶液进行，以测试多囊泡释放的要求以及 pH 在控制囊泡回收率中的作用。将开发计算工具，用于分析复杂诱发释放事件期间胞吐作用的瞬时速率，以及对胞吐作用后立即进行的突触前 pH 动态建模。这些实验的结果有可能揭示分子机制和信号传导策略，不仅对于听觉感知过程很重要，而且对于感觉神经元如何编码和维持描述广泛刺激特征的信息丰富的信号的一般理解也很重要。