Dendritic Integration and Synaptic Plasticity in the MSO

MSO 中的树突整合和突触可塑性

• 批准号: 10316175
• 负责人: Nace L Golding
• 金额: $ 43.03万
• 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 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10316175
• 关键词: 3-Dimensional; Ablation; Acoustics; Action Potentials; Address; Affect; Agreement; Anatomy; Antibodies; Area; Auditory; Auditory Prosthesis; Axon; Binaural; Birds; Brain; Brain Stem; Caliber; Cell Nucleus; Cells; Child; Clinical; Closure by clamp; Cochlea; Code; Cues; Data; Dendrites; Detection; Development; Developmental Process; Ear; Electrophysiology (science); Environment; Exhibits; Fire - disasters; Fluorescence; Foundations; Frequencies; Generations; Gerbils; Goals; Hearing; Human; In Vitro; Injections; Ion Channel Gating; Language Development; Lateral; Light; Lighting; Location; Mammals; Measures; Medial; Membrane; Modeling; Morphology; Neurons; Optics; Outcomes Research; Pattern; Phenotype; Physiological; Play; Positioning Attribute; Potassium Channel; Process; Property; Research; Resolution; Role; Sensorineural Hearing Loss; Shapes; Slice; Sodium Channel; Sound Localization; Speech; Speech Discrimination; Speech Perception; Stimulus; Structure; Synaptic plasticity; Testing; Time; Variant; base; binaural hearing; biophysical properties; cell type; channel blockers; deafness; density; electrical property; experience; experimental study; hearing impairment; ion channel blocker; large datasets; medial superior olive; neural patterning; neuronal cell body; normal hearing; patch clamp; receptive field; sound; theories; voltage; voltage clamp; voltage gated channel

Project Summary Humans and other mammals use the temporal fine structure in sounds to identify and help localize auditory objects in three-dimensional space. The broad goal of this research is both to understand how sound localization cues are processed in the brain as well as to understand how neurons in the underlying circuitry acquire the appropriate biophysical properties during development. 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 horizontal sound localization as well as for understanding speech patterns in noisy environments. ITDs are computed in the MSO via the process of coincidence detection, in which the simultaneous arrival of excitatory inputs from the two ears is detected and conveyed through action potential firing with a time resolution of a few tens of microseconds. The neurons of the MSO have historically been assumed to be functionally and morphologically homogeneous. However, our preliminary data refutes this simplistic view of the MSO: we hypothesize instead that variation in dendritic morphology and electrical properties critically shapes the location of spatial receptive fields, and that these differences are in part influenced after hearing onset by the level and pattern of neural activity. We will address these questions by combining paired dendritic and somatic patch recordings, compartmental modeling, patterned LED illumination of light-sensitive channel blockers, and hearing manipulations. Aim 1 will address the functional significance of the newly discovered tonotopic diversity in electophysiological properties of MSO neurons both in vitro using patch- clamp recordings. Aim 2 will extend these analyses to understand how the functional diversity in MSO neurons is conferred by differences in the expression levels and properties of voltage-gated channels in the axon initial segment. Aim 3 will explore how the diversity of dendritic structure itself shapes the temporal requirements for optimal detection of binaural coincidence. The information from these experiments will increase our understanding of the mechanisms underlying spatial hearing in mammals, as well as the developmental processes that control the formation of a critical circuit component in the MSO. As binaural hearing is important for speech perception and language acquisition in children, a mechanistic understanding of binaural circuit function and development may ultimately inform clinical strategies for addressing hearing impairments.

项目摘要 人类和其他哺乳动物在声音中使用时间精细结构来识别和帮助 将听觉对象定位在三维空间中。这项研究的广泛目标是 了解如何在大脑中处理声音本地化线索以及了解如何 基础电路中的神经元在发育过程中获得了适当的生物物理特性。 该提议着重于内侧上级橄榄（MSO），这是处理的第一个和关键阶段 两只耳朵的室内时间差异（ITD），用于水平声音定位的提示 以及了解嘈杂环境中的语音模式。 ITD通过MSO通过 巧合检测的过程，其中同时从两者中同时到达兴奋性输入 通过动作电势射击检测和传达耳朵，并分辨出几十个时间分辨率 微秒。 历史上，MSO的神经元在功能和形态上被认为是 同质。但是，我们的初步数据驳斥了对MSO的简单观点：我们假设 相反 空间接受场，并且这些差异部分受到听力发作后的影响 和神经活动的模式。我们将通过结合配对的树突和躯体来解决这些问题 补丁记录，隔室建模，光敏通道的图案化LED照明 阻滞剂和听力操纵。 AIM 1将解决新的功能意义 使用斑块 - 夹具记录。 AIM 2将扩展这些分析，以了解MSO的功能多样性如何 神经元是由电压门控通道的表达水平和性能差异赋予的 轴突初始段。 AIM 3将探讨树突结构的多样性本身如何塑造 最佳检测双耳巧合的时间要求。 这些实验的信息将增加我们对机制的理解 哺乳动物中的基本空间听力以及控制的发展过程 MSO中临界电路组件的形成。由于双耳听证对于语音很重要 儿童的感知和语言获取，对双耳电路功能的机械理解 开发最终可能会为解决听力障碍的临床策略提供信息。

项目成果

In vivo coincidence detection in mammalian sound localization generates phase delays.

• DOI: 10.1038/nn.3948
• 发表时间: 2015-03
• 期刊: NATURE NEUROSCIENCE
• 影响因子: 25
• 作者: Franken, Tom P.;Roberts, Michael T.;Wei, Liting;Golding, Nace L.;Joris, Philip X.
• 通讯作者: Joris, Philip X.

Glycinergic Inhibitory Plasticity in Binaural Neurons Is Cumulative and Gated by Developmental Changes in Action Potential Backpropagation.

双耳神经元中的甘氨酸能抑制可塑性是累积的，并由动作电位反向传播的发育变化控制。

• DOI: 10.1016/j.neuron.2018.03.001
• 发表时间: 2018
• 期刊: Neuron
• 影响因子: 16.2
• 作者: Winters,BradleyD;Golding,NaceL
• 通讯作者: Golding,NaceL

Amplitude Normalization of Dendritic EPSPs at the Soma of Binaural Coincidence Detector Neurons of the Medial Superior Olive.

内侧上橄榄双耳符合检测器神经元体树突 EPSP 的振幅标准化。

• DOI: 10.1523/jneurosci.3110-16.2017
• 发表时间: 2017
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Winters,BradleyD;Jin,Shan-Xue;Ledford,KennethR;Golding,NaceL
• 通讯作者: Golding,NaceL

An essential role for modulation of hyperpolarization-activated current in the development of binaural temporal precision.

• DOI: 10.1523/jneurosci.3882-11.2012
• 发表时间: 2012-02-22
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Khurana S;Liu Z;Lewis AS;Rosa K;Chetkovich D;Golding NL
• 通讯作者: Golding NL

A mechanistic understanding of the role of feedforward inhibition in the mammalian sound localization circuitry.

• DOI: 10.1016/j.neuron.2013.04.022
• 发表时间: 2013-06-05
• 期刊: Neuron
• 影响因子: 16.2
• 作者: Roberts MT;Seeman SC;Golding NL
• 通讯作者: Golding NL