Regulation of Synaptic Vesicle Dynamics in the Auditory System

听觉系统突触小泡动力学的调节

• 批准号: 9479765
• 负责人: Samuel Matthew Young
• 金额: $ 38.13万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9479765
• 关键词: Acoustics; Action Potentials; Affect; Auditory; Auditory system; Binaural; Biological Neural Networks; Brain; Brain Injuries; Brain Stem; Cell Nucleus; Cells; Chemicals; Cochlear nucleus; Communication; Coupled; Data; Diglycerides; Electrophysiology (science); Ensure; F-Actin; Frequencies; Functional disorder; G protein coupled receptor kinase; GIT1 gene; GIT2 gene; Glutamates; Goals; Homologous Gene; Hybrids; Immune; Kinetics; Knock-out; Knockout Mice; Lead; Learning; Medial; Molecular; Neurodegenerative Disorders; Neurons; Pathway interactions; Pattern; Phorbol Esters; Physiological; Presynaptic Terminals; Probability; Protein Isoforms; Proteins; Publishing; Recovery; Recycling; Regulation; Regulatory Pathway; Reporting; Role; Second Messenger Systems; Signal Transduction; Slice; Stimulus; Synapses; Synaptic Transmission; Synaptic Vesicles; Technology; Testing; Time; Training; Transgenic Mice; Viral Vector; Work; auditory processing; biophysical techniques; in vivo; information processing; insight; molecular domain; mutant; neural circuit; neuronal circuitry; neuropsychiatric disorder; neurotransmission; operation; postsynaptic; presynaptic; public health relevance; receptor; response; sound; synaptic depression; synaptic function; transmission process; trapezoid body; vesicular release; voltage

 DESCRIPTION (provided by applicant): Our long term goal is to understand the mechanisms of synaptic vesicle release and recovery that permit the accurate encoding of sound over wide dynamic ranges over varying times scales. The calyx of Held/MNTB synapse in the auditory brainstem is a key connection in this pathway since it provides precise timing and activates sustained inhibition to key binaural cell groups. Its large size has made it an experimentally accessible entry point into understanding the mechanisms and function of these synaptic connections. The calyx can be driven by sound at high rates, operates in the background of varying spontaneous firing rates, and yet must be relatively immune to acoustically noisy backgrounds. How is this achieved? Since the presynapse has a finite supply of fusion competent synaptic vesicles (SVs), termed the readily releasable pool (RRP), the release and replenishment of the RRP must be balanced to sustain transmission. Priming, the creation of fusion competent SVs at the active zone (AZ) that can be released in response to action potentials (APs), is a key regulatory pathway that regulates the RRP release and replenishment to sustain transmitter release. Ultimately, the molecular mechanisms that regulate priming underlie efficient release and replenishment of SVs underpins sound encoding. Therefore we aim to define the molecular mechanisms that ensure availability of release competent SVs throughout a wide range of AP firing rates to support the early stages of auditory processing. As release and replenishment of the RRP is necessary in all synapses to encode information over varying timescales, our data will have broad relevance to understanding how synaptic communication leads to information transfer in neural networks.

 描述（由适用提供）：我们的长期目标是了解突触场地释放和恢复的机制，这些机制允许在不同时间尺度上精确编码声音在宽动态范围内进行精确编码。听觉脑干中持有/MNTB突触的花萼是该途径中的关键连接，因为它提供了精确的时机并激活对关键双耳细胞组的持续抑制作用。它的大尺寸使其成为理解这些合成连接的机制和功能的实验可访问的入口点。花萼可以以高速速度驱动，在不同赞助率的背景下运行，但必须相对免疫准确的噪声背景。这是如何实现的？由于肿瘤前的融合供应有限的融合合成蔬菜（SVS），称为容易释放的池（RRP），因此释放和补充了RRP启动，因此可以在Active区（AZ）释放融合有能力的SVS的SVS创建，以释放响应动作电位（APS）的释放（APS），是对维护的启动，是对密钥调节的启动。最终，调节启动启动的分子机制是有效释放和SVS基础的复制胶体化的基础。因此，我们旨在定义分子机制，以确保在广泛的AP触发速率中释放有能力的SV，以支持听觉处理的早期阶段。在所有突触中都必须释放和补充RRP来编码有关不同时间尺度的信息，因此我们的数据将与了解合成通信如何导致神经网络中的信息传递有关。