Dendritic integration and synaptic plasticity in the MSO

MSO 中的树突整合和突触可塑性

• 批准号: 8516491
• 负责人: Nace L Golding
• 金额: $ 30.65万
• 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/8516491
• 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.

描述（由申请人提供）：快速、时变的声音特征对于人类和其他哺乳动物定位声源以及解释语音和交流呼叫至关重要。这项研究的主要目标是了解这些特征是如何在大脑中处理的，以及理解听觉回路中的神经元是如何在发育过程中获得适当的生物物理特性来进行这些计算的。这一建议的重点是内侧上橄榄（MSO），这是处理来自两耳的耳间时差（ITDs）的第一个也是关键阶段，用于沿水平面定位声音的线索。在MSO中，通过重合检测过程计算和传递过渡段，通过该过程，来自两个耳朵的兴奋输入被分离到双极树突杆的不同分支上，并以亚毫秒的时间分辨率在soma上相加。因此，要理解声音定位线索是如何在MSO中处理的，就需要了解突触输入的时间和强度是如何在两组树突中控制的。本研究将探讨MSO神经元快速时间处理能力的发展不是预先编程的，而是在听力开始后由突触和放电活动驱动的假设。我们将通过结合树突斑块记录、双光子和宽视场钙成像和解剖学技术来探索这一假设。目的1将研究轴突初始段在发育过程中形成发射特性的特征和作用。Aim 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，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体验过程中发生改变。来自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的听觉活动也很重要。