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定位声源以及解释语音和通信呼叫至关重要。这项研究的总体目标是了解这些特征在大脑中是如何处理的，以及了解听觉回路中的神经元如何在发育过程中获得适当的生物物理特性来执行这些计算。该提案重点关注内侧上橄榄（MSO），即第一阶段和关键阶段 用于处理两耳的耳间时间差 (ITD)，这些线索用于沿水平面定位声音。在 MSO 中，ITD 通过重合检测过程进行计算和传送，通过该过程，来自两只耳朵的兴奋性输入被分离到双极树突乔木的不同分支上，并以亚毫秒时间分辨率在体细胞上求和。因此了解声音定位线索是如何产生的 在 MSO 中进行处理又需要了解如何在两组树突中控制突触输入的时间和强度。该提案将研究这样的假设：MSO 神经元的快速时间处理能力的发展不是预先编程的，而是在听觉开始后由突触和放电活动驱动的。我们将通过结合树突斑片记录、2 光子和 宽视野钙成像和解剖技术。目标 1 将研究轴突初始段的特征和在发育过程中塑造发射特性中的作用。目标 2 将研究突触活动如何通过超极化激活的阳离子通道的变化转化为增加的内在神经元精度，目标 3 将揭示沿 MSO 树突的兴奋性突触强度的空间模式以及该模式是否在过程中发生改变 早期的听觉体验。这些实验的信息不仅对于理解哺乳动物听力的基本机制很重要，而且对于理解正常听觉发育的改变（例如通过听力缺陷或耳聋）如何塑造听觉回路的功能以及这些回路如何响应通过听觉假体重新引入听觉活动非常重要。 公共健康相关性：在上橄榄核中，声音定位线索和语音信号的编码关键取决于快速而精确的内在膜特性的发展。因此，从机制上理解这些特性如何受到早期听觉体验的控制，对于理解大脑如何受到听力损失、耳聋和听觉假肢装置的引入的影响非常重要。