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

• 批准号: 8034018
• 负责人: Armin Harry Seidl
• 金额: $ 15.6万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-01 至 2013-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8034018
• 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' 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; reconstruction; repaired; research study; sample fixation; segregation; sound; sound frequency; superior olivary nucleus; tool; voltage

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. PUBLIC HEALTH RELEVANCE: Understanding the mechanisms of binaural perception requires detailed analyses of the neural circuitry responsible for the analysis of interaural time differences (ITDs), the main cues for low frequency sound localization and segregation of speech in noise. The objective of this project is to provide a detailed analysis of the biophysical nature of the circuit responsible for ITD coding in the mammalian brainstem. Understanding this mechanism will provide a solid foundation to better understand hearing disabilities and will assist in finding ways to solve hearing related health issues.

描述（由申请人提供）：出于临床（检测噪声中的语音）和基础神经生物学（计算）原因，了解哺乳动物低频声音定位的精确机制非常有意义。这些机制背后的脑干回路已被广泛研究，并且最近引起了听觉神经科学家界的新兴趣。传统上，根据 Jeffress 50 多年前提出的模型，该电路被认为体现了延迟线系统，但由于其时间精确的抑制输入，该电路最近受到讨论，因此提出了替代机制。我相信我可以通过这里提出的实验为这个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，解剖学传导速度参数可以补偿轴突长度差异。这使我对哺乳动物低频声音定位电路中的生理延迟线系统产生了一个新的假设。代替轴突长度，诸如轴突直径、髓鞘厚度和节间距离等传导速度参数可以提供显着且系统的功能变化，以创建传导时间梯度。此外，传导速度参数的差异表达可能负责该系统在微秒范围内的时间精确调谐，这对于沿方位角不同位置产生的双耳声音的重合检测至关重要。 该研究计划的目标是准确测量轴突长度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。我假设在哺乳动物低频声音定位电路中，除了轴突长度之外还有更多的特征会产生时间延迟。我认为生物物理特性有助于 ITD 编码的生理延迟，并创建该电路机制所需的精确计时。我将测量沙鼠从前腹侧耳蜗核 (AVCN) 神经元延伸到同侧和对侧内侧上橄榄核 (MSO) 的单个轴突的总长度。此外，我将确定轴突直径、髓鞘厚度以及 AVCN 轴突不同节段战略位置处的 Ranvier 节点之间的距离。最后，我将测量特定轴突片段的传导速度，并将其与解剖学发现相关联。这些实验将使人们进一步了解这一重要的大脑机制，并将提供实验测试调节差异轴突特征对于巧合检测系统开发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和解决听力相关问题的工具提供基础。 公共健康相关性：了解双耳感知机制需要对负责分析耳间时间差 (ITD) 的神经回路进行详细分析，ITD 是低频声音定位和噪声中语音分离的主要线索。该项目的目标是对哺乳动物脑干中负责 ITD 编码的电路的生物物理性质进行详细分析。了解这一机制将为更好地了解听力障碍提供坚实的基础，并有助于找到解决听力相关健康问题的方法。