Dendritic integration and synaptic plasticity in the MSO

MSO 中的树突整合和突触可塑性

• 批准号: 8387949
• 负责人: Nace L Golding
• 金额: $ 31.57万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8387949
• 关键词: AMPA Receptors; Accounting; Action Potentials; Affect; Auditory; Axon; Biophysics; Brain; Brain Stem; Calcium; Cations; Cell Nucleus; Cells; Characteristics; Cochlear Implants; Code; Communication; Conductive hearing loss; Confocal Microscopy; Cueing for speech; Cues; Data; Dendrites; Detection; Development; Ear; Excitatory Synapse; Exhibits; Financial compensation; Gated Ion Channel; Gerbils; Glutamates; Goals; Hearing; Human; Image; Interphase Cell; Ion Channel; Knowledge; Laser Scanning Microscopy; Link; Location; Mammals; Maps; Medial; Membrane; N-Methyl-D-Aspartate Receptors; Neurons; Noise; Olives - dietary; Optics; Outcomes Research; Patch-Clamp Techniques; Pattern; Photons; Plastics; Potassium Channel; Process; Property; Prosthesis; Regulation; Research; Resolution; Rest; Role; Shapes; Signal Transduction; Slice; Sodium Channel; Sound Localization; Source; Speech; Speed; Staging; Stimulus; Sum; Synapses; Synaptic plasticity; Techniques; Testing; Time; Translating; attenuation; channel blockers; deafness; density; electrical property; experience; hearing impairment; hyperpolarization-activated cation channel; in vivo; insight; neuronal cell body; novel; research study; sound; stem; tool; voltage; voltage clamp; voltage gated channel

DESCRIPTION (provided by applicant: Fast, time-varying features of sound are essential for humans and other mammals for localizing sound sources as well interpreting speech and communication calls. The broad goal of this research is both to understand how these features are processed in the brain, as well as to understand how neurons in auditory circuits acquire the appropriate biophysical properties during development to carry out these computations. This proposal focuses on the medial superior olive (MSO), the first and critical stage for processing interaural time differences (ITDs) from the two ears, cues that are used for localizing sounds along the horizontal plane. In the MSO, ITDs are computed and conveyed through the process of coincidence detection, by which excitatory inputs from the two ears are segregated onto different branches of a bipolar dendritic arbor and sum at the soma with submillisecond time resolution. Thus an understanding of how sound localization cues are processed in the MSO in turn requires knowledge of how the timing and strength of synaptic inputs are controlled in the two sets of dendrites. This proposal will investigate the hypothesis that the development of fast time-processing capabilities in MSO neurons is not preprogrammed, but is driven after hearing onset by synaptic and firing activity. We will explore this hypothesis by combining dendritic patch recordings, 2-photon and wide-field calcium imaging and anatomical techniques. Aim 1 will examine the characteristics and role of the axon initial segment in shaping firing characteristics during development. Aim 2 will examine how synaptic activity is translated into increasing intrinsic neuronal precision, via changes in hyperpolarization-activated cation channels, and Aim 3 will reveal the spatial pattern of excitatory synapse strength along MSO dendrites and whether this pattern is altered during the course of early auditory experience. The information from these experiments is important not only for understanding basic mechanisms of mammalian hearing but also for understanding how alterations of normal auditory development (e.g. via hearing deficits or deafness) shape the function of auditory circuits and how these circuits respond to the reintroduction of auditory activity via auditory prostheses. PUBLIC HEALTH RELEVANCE: In the medial superior olive, the encoding of sound localization cues and speech signals depends critically on the development of intrinsic membrane properties that are both fast and precise. A mechanistic understanding of how these properties are governed by early auditory experience is thus important for understanding how the brain is affected by hearing loss, deafness, and the introduction of auditory prosthetic devices.

描述（由申请人提供：声音的快速，随时间变化的特征对于人类和其他哺乳动物进行本地化来源以及解释语音和沟通电话。这项研究的广泛目标是了解这些特征如何在大脑中处理这些特征，以及如何在开发过程中在开发过程中如何在开发过程中进行适当的生物物质，以便在这些计算机上进行适当的生物物质，并如何进行计算。为了处理两个耳朵的间隔时间差异（ITD），用于在MSO中定位的声音，通过重合检测过程进行计算并传达ITD。反过来，在MSO中处理的是如何在两组树突中控制突触输入的时间和强度。该提案将调查以下假设：MSO神经元中快速处理能力的发展没有预编程，而是通过突触和发射活动听到发作后驱动的。我们将通过结合树突状斑块记录，2光子和宽场钙成像和解剖技术来探讨这一假设。 AIM 1将检查轴突初始段在塑造开发过程中的发射特征中的特征和作用。 AIM 2将检查突触活动如何通过变化超极化激活的阳离子通道的变化转化为内在的神经元精度，而AIM 3将揭示沿MSO树突的兴奋性突触强度的空间模式，以及这种模式是否在早期听觉经历过程中改变了。这些实验中的信息不仅对于理解哺乳动物听力的基本机制也很重要，而且对于理解正常听觉发展的变化（例如，通过听力不足或耳聋）如何塑造听觉电路的功能以及这些电路如何通过听觉专业人士对听觉活动的重新引入。 公共卫生相关性：在上级橄榄中，声音本地化提示和语音信号的编码主要取决于既快速又精确的内在膜特性的发展。因此，对这些特性如何受早期听觉经验支配的机械理解对于理解大脑如何受到听力丧失，耳聋和听觉假体设备的引入而言，这一点很重要。