Morphometric and physiologic analyses of the mammalian low frequency sound locali

哺乳动物低频声音局部的形态测量和生理分析

基本信息

批准号：
8374382
负责人：
Armin Harry Seidl
金额：
$ 14.82万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-12-01 至 2014-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8374382
关键词：
3-Dimensional Action Potentials Acute Antibodies Auditory Axon Ballistics Bathing Binding Birds Brain Brain Stem Caliber Characteristics Clinical Cochlear nucleus Code Communities Computer software Contralateral Cues Detection Development Dimensions Electrons Electroporation Fiber Fluorescence Fluorescence Resonance Energy Transfer Fluorescent Dyes Foundations Frequencies Gerbils Goals Health Hearing Image Individual Ipsilateral Label Lead Length Light Measurement Measures Medial Membrane Methods Microscope Microscopic Modeling Myelin Myelin Sheath Nature Neurobiology Neurons Noise Optics Pathway interactions Pattern Perception Physiological Plastics Positioning Attribute Preparation Property Proteins Ranvier&apos s Nodes Regulation Research Scanning Side Signal Transduction Slice Solid Sound Localization Speech Speed System Techniques Testing Thick Three-Dimensional Image Time Travel Variant analog attenuation base dipicrylamine disability imaging modality interest neural circuit neuronal cell body novel programs public health relevance reconstruction repaired research study sample fixation segregation sound sound frequency superior olivary nucleus tool voltage

项目摘要

DESCRIPTION (provided by applicant): Understanding the precise mechanisms underlying mammalian low frequency sound localization is of much interest for both clinical (detecting speech in noise) and fundamental neurobiology (computational) reasons. The brainstem circuit underlying these mechanisms has been extensively studied and has lately enjoyed new interest among the community of auditory neuroscientists. Traditionally considered to embody a delay line system according to a model proposed over 50 years ago by Jeffress, this circuit has recently come under discussion because of its temporally precise inhibitory inputs and thus alternative mechanisms have been suggested. I believe I can contribute important new information to this topic by the experiments proposed here. Our recent studies of the avian sound localization circuit clearly show that anatomical conduction velocity parameters can compensate for axon length differences. This led me to a new hypothesis about a physiological delay line system in the mammalian low frequency sound localization circuit. Instead of axon length, conduction velocity parameters such as axon diameter, myelin sheath thickness and internode distances may provide significant and systematic functional variations toward creating a gradient of conduction times. Moreover, differential expression in conduction velocity parameters might be responsible for the temporally precise tuning of this system in the microsecond range, essential for coincidence detection of binaural sounds arising from different positions along the azimuth. The goal of this proposed research program is to make accurate measurements of axon length and to assess biophysical properties responsible for conduction velocity in the mammalian low frequency sound localization circuit. I hypothesize that in the mammalian low frequency sound localization circuit more features than just axon length create temporal delays. I propose that biophysical properties contribute to physiological delays in ITD coding and create the precise timing needed for the mechanism of this circuit. I will measure total length of individual axons extending from neurons in the anteroventral cochlear nucleus (AVCN) to the ipsilateral and the contralateral medial superior olivary nuclei (MSOs) in the gerbil. Additionally, I will determine axon diameter, myelin sheath thickness and distances between Nodes of Ranvier at strategic position along different segments of the AVCN axon. Finally, I will measure conduction velocities in specific axon segments and correlate them with the anatomical findings. These experiments will enable further understanding of this important brain mechanism and will provide the baseline information needed to experimentally test the importance of the regulation differential axonal characteristics for the development of coincidence detection systems. Ultimately this research will provide a basis to develop tools to repair hearing disabilities and to solve hearing related problems.

描述（由申请人提供）：了解哺乳动物低频声音定位的确切机制对于临床（噪声中的检测语音）和基本神经生物学（计算）原因引起了人们的关注。这些机制的脑干电路已经进行了广泛的研究，最近在听觉神经科学家社区中享有新的兴趣。传统上，根据杰弗雷斯（Jeffress）在50年前提出的模型中体现延迟线系统，该电路最近因其时间精确的抑制输入而进行了讨论，因此提出了替代机制。我相信我可以通过此处提出的实验为该主题贡献重要的新信息。我们最近对鸟类声音定位电路的研究清楚地表明，解剖传导速度参数可以补偿轴突长度差异。这使我提出了关于哺乳动物低频声音定位电路中生理延迟线系统的新假设。代替轴突长度，传导速度参数（例如轴突直径），髓鞘的厚度和节间距离可能会提供显着的系统功能变化，以创建传导时间的梯度。此外，传导速度参数中的差分表达可能是在微秒范围内对该系统进行时间精确调整的原因，这对于沿着方位角的不同位置引起的双耳声音的巧合检测至关重要。该提出的研究计划的目的是对轴突长度进行准确的测量，并评估负责哺乳动物低频声音定位电路传导速度的生物物理特性。我假设在哺乳动物的低频声音定位电路中，不仅仅是轴突长度会产生时间延迟。我建议生物物理特性有助于ITD编码中的生理延迟，并创建该电路机理所需的精确时机。我将测量从前腹耳蜗核（AVCN）中延伸到同侧的单个轴突的总长度，并在Gerbil中的同侧和对侧内侧上橄榄核（MSO）。此外，我将确定轴突直径，髓鞘鞘的厚度以及沿AVCN轴突不同片段的战略位置的Ranvier节点之间的距离。最后，我将测量特定轴突段中的传导速度，并将其与解剖学发现相关联。这些实验将进一步了解这种重要的大脑机制，并将提供实验测试调节差异轴突特征在开发巧合检测系统的重要性所需的基线信息。最终，这项研究将为开发修复听力障碍并解决与听力有关的问题的工具提供基础。