Synaptic mechanisms of auditory information processing

听觉信息处理的突触机制

• 批准号: 10369617
• 负责人: Hai Huang
• 金额: $ 32.3万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10369617
• 关键词: Action Potentials; Affect; Attention; Auditory; Auditory system; Brain Stem; Cell membrane; Complex; Cytosol; Data; Dialysis procedure; Dyes; Electric Capacitance; Endocytosis; Environment; Exocytosis; Frequencies; Future; Glutamates; Goals; Hearing problem; Image; Injury; Link; Maps; Measurement; Membrane; Methods; Modeling; Neurons; Neurotransmitters; Pathologic; Pharmacology; Phase; Physiological; Probability; Process; Property; Recycling; Regulation; Research; Role; Signal Transduction; Site; Synapses; Synaptic Transmission; Synaptic Vesicles; Vesicle; Work; falls; hearing impairment; information processing; insight; neurotransmitter release; neurotransmitter transport; noise exposure; normal hearing; postsynaptic; presynaptic; quantum; sound frequency; synaptic function; transmission process; treatment strategy; uptake; vesicular release

PROJECT SUMMARY The reliability and precision of synaptic transmission are required in circuits of the auditory brainstem in order to encode timing with submillisecond accuracy. Auditory information is encoded by action potentials phase-locked to sound frequency at high rates. Accordingly, synaptic vesicles need to be recycled and refilled rapidly. Accumulating studies have uncovered the processes of vesicle fusion and recycling; however, the control of the contents of synaptic vesicles has received considerably less attention. Reasons for this gap in our understanding include the small size of synaptic vesicles and of conventional synapses, the complex ionic basis for loading of neurotransmitter into vesicles, and the difficulty in manipulating and assessing vesicle loading in physiological conditions. We have recently found that a Na+/H+ exchanger expressed on synaptic vesicles promotes vesicle filling with glutamate. Using the calyx of Held, a giant glutamatergic synapse in the auditory brainstem that permits direct pre- and postsynaptic recordings and manipulation of the presynaptic cytosol, we showed that glutamate loading is facilitated by intracellular Na+ over the physiological concentration range. Na+ influx through presynaptic plasma membrane HCN channels affects presynaptic Na+ concentration, regulates glutamate uptake, and thus controls miniature excitatory postsynaptic currents. Here we propose that during high-frequency signaling, when large amounts of glutamate are released, Na+ accumulates in terminals and facilitates glutamate uptake into synaptic vesicle, accelerating vesicle replenishment and sustaining reliable synaptic transmission. We further hypothesize that the control of vesicle loading, release and recycling can be affected by hearing loss. This work will establish a new fundamental role of Na+ to link activity and synaptic function under physiological and pathological conditions.

项目摘要 听觉脑干回路需要突触传递的可靠性和精确性，以便 以亚毫秒精度编码定时。听觉信息是由动作电位锁相编码的 以高速率传输到声音频率。因此，突触囊泡需要被迅速回收和重新填充。 越来越多的研究已经揭示了囊泡融合和再循环的过程;然而， 突触囊泡的内容物受到的关注相当少。我们理解上的差距的原因 包括突触囊泡和常规突触的小尺寸， 神经递质进入囊泡，以及难以操纵和评估囊泡负荷的生理 条件我们最近发现，突触囊泡上表达的Na+/H+交换体促进突触囊泡的形成。 充满谷氨酸盐利用Held的萼，听觉脑干中的一个巨大的神经元突触， 允许直接的突触前和突触后记录和操纵突触前细胞质，我们表明， 在生理浓度范围内，细胞内Na+促进谷氨酸盐的加载。Na+通过 突触前质膜HCN通道影响突触前Na+浓度，调节谷氨酸摄取， 从而控制微小的兴奋性突触后电流。在这里，我们建议，在高频率 当大量的谷氨酸被释放时，Na+在末端积累， 摄取进入突触囊泡，加速囊泡补充和维持可靠的突触传递。 我们进一步假设，控制囊泡加载，释放和回收可以通过听力损失的影响。 这项工作将建立一个新的基础作用Na+连接活动和突触功能的生理条件下， 和病理状况。