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.

项目概要 人类和其他哺乳动物利用声音中的时间精细结构来识别和帮助 在三维空间中定位听觉对象。这项研究的总体目标是 了解声音定位线索在大脑中的处理方式以及如何 底层电路中的神经元在发育过程中获得适当的生物物理特性。 该提案重点关注内侧上橄榄 (MSO)，这是加工的第一个也是关键的阶段 两耳的耳间时间差 (ITD)，用于水平声音定位的提示 以及理解嘈杂环境中的语音模式。 ITD 在 MSO 中通过以下方式计算 重合检测的过程，其中来自两个的兴奋性输入同时到达 耳朵通过动作电位发射进行检测和传达，时间分辨率为几十秒 微秒。 MSO 的神经元历来被认为在功能和形态上 同质。然而，我们的初步数据反驳了 MSO 的这种简单化观点：我们假设 相反，树突形态和电性能的变化关键地决定了 空间感受野，并且这些差异在听力开始后部分受到水平的影响 和神经活动模式。我们将通过结合成对的树突状细胞和体细胞来解决这些问题 斑块记录、区室建模、光敏通道的图案化 LED 照明 阻滞剂和听力操纵。目标 1 将解决新的功能意义 使用贴片在体外发现了 MSO 神经元电生理特性的音调多样性 钳位录音。目标 2 将扩展这些分析，以了解 MSO 中的功能多样性如何 神经元的差异是由电压门控通道的表达水平和特性的差异决定的。 轴突起始段。目标 3 将探索树突结构本身的多样性如何塑造 双耳重合最佳检测的时间要求。 这些实验的信息将增加我们对机制的理解 哺乳动物的潜在空间听觉，以及控制听觉的发育过程 MSO 中关键电路组件的形成。由于双耳听力对于言语很重要 儿童的感知和语言习得，双耳回路功能的机械理解 发展可能最终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

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

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

Perisomatic voltage-gated sodium channels actively maintain linear synaptic integration in principal neurons of the medial superior olive.

• DOI: 10.1523/jneurosci.2385-09.2010
• 发表时间: 2010-02-10
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Scott LL;Mathews PJ;Golding NL
• 通讯作者: Golding NL