Synaptic mechanisms of auditory information processing

听觉信息处理的突触机制

• 批准号: 10132290
• 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 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10132290
• 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; Noise; 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; 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 在听觉脑干的电路中需要突触传输的可靠性和精度才能 用亚亚数精度编码计时。听觉信息由动作电位相锁编码 以高速频率进行音频。因此，需要迅速对突触囊泡进行回收和补充。 积累的研究发现了囊泡融合和回收的过程。但是，控制 突触囊泡的含量已受到大大减少的关注。我们理解的差距的原因 包括小尺寸的突触囊泡和常规突触，加载的复杂离子基础 神经递质进入囊泡，以及在生理学中操纵和评估囊泡负荷的困难 状况。我们最近发现，在突触囊泡上表达的Na+/H+交换器促进了囊泡 充满谷氨酸。使用Hold的花萼，在听觉脑干中的巨型谷氨酸能突触 允许直接和突触后记录以及突触前细胞质的操纵，我们表明 在生理浓度范围内，细胞内Na+促进谷氨酸负荷。 Na+涌入 突触前质膜HCN通道影响突触前Na+浓度，调节谷氨酸摄取， 从而控制微型兴奋性突触后电流。在这里，我们建议在高频期间 信号传导，当释放大量谷氨酸时，Na+在末端积聚并促进谷氨酸 吸收突触囊泡，加速囊泡补充并维持可靠的突触传播。 我们进一步假设，囊泡载荷，释放和回收的控制可能会受到听力损失的影响。 这项工作将确定Na+在生理下连接活动和突触功能的新基本作用 和病理状况。