Morphometric and physiologic analyses of the mammalian low frequency sound locali

描述（由申请人提供）：由于临床（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趣。这些机制背后的脑干回路已经被广泛研究，最近在听觉神经科学家群体中引起了新的兴趣。传统上被认为是体现延迟线系统根据Jeffress在50年前提出的模型，这个电路最近受到讨论，因为它的时间精确的抑制性输入，从而替代机制已被建议。我相信我可以通过这里提出的实验为这个主题提供重要的新信息。 我们最近对鸟类声音定位回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。这使我对哺乳动物低频声音定位电路中的生理延迟线系统提出了一个新的假设。代替轴突长度，传导速度参数（诸如轴突直径、髓鞘厚度和节间距离）可以提供朝向产生传导时间梯度的显著和系统的功能变化。此外，在传导速度参数的差分表达式可能是负责在微秒范围内的时间上精确调谐该系统，必不可少的从不同位置沿沿着的双耳声音的重合检测。 这项研究计划的目标是精确测量轴突长度，并评估生物物理特性负责传导速度在哺乳动物低频声音定位电路。我假设，在哺乳动物的低频声音定位电路更多的功能，而不仅仅是轴突长度创建时间延迟。我建议，生物物理特性有助于ITD编码的生理延迟，并创建该电路的机制所需的精确定时。我将测量从前腹侧耳蜗核（AVCN）的神经元延伸到同侧和对侧内侧上级橄榄核（MSO）的沙鼠的单个轴突的总长度。此外，我将确定轴突直径，髓鞘厚度和Ranvier节点之间的距离在战略位置沿着不同节段的AVCN轴突。最后，我将测量特定轴突段的传导速度，并将其与解剖学结果相关联。这些实验将使进一步了解这一重要的大脑机制，并将提供所需的基线信息，以实验测试的重要性，调节差异轴突特性的发展的重合检测系统。最终，本研究将为开发听力障碍修复工具和解决听力相关问题提供基础。

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.