Morphometric and physiologic analyses of the mammalian low frequency sound locali

描述(由申请人提供)：了解哺乳动物低频声音定位的精确机制对于临床(检测噪声中的语音)和基本神经生物学(计算)都很有意义。这些机制背后的脑干回路已经得到了广泛的研究，最近在听觉神经科学家群体中引起了新的兴趣。根据Jeffress 50多年前提出的模型，传统上被认为是包含延迟线系统的这种电路，最近因为其时间上精确的抑制输入而受到讨论，因此提出了替代机制。我相信，通过这里提出的实验，我可以为这个课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的差异。这让我对哺乳动物低频声音定位回路中的生理延迟线系统提出了一个新的假设。除了轴突长度，轴突直径、髓鞘厚度和节间距离等传导速度参数可能会提供显著的系统性功能差异，从而产生传导时间的梯度。此外，传导速度参数的不同表达可能是该系统在微秒范围内的时间精确调谐的原因，这对于沿方位向不同位置发出的双耳声音的符合检测至关重要。 这项拟议的研究计划的目标是准确测量轴突长度，并评估哺乳动物低频声音定位电路中负责传导速度的生物物理性质。我假设，在哺乳动物的低频声音定位回路中，除了轴突长度之外，还有更多的特征会造成时间延迟。我认为生物物理特性导致了ITD编码的生理延迟，并创造了这一电路机制所需的精确计时。我将测量沙土鼠单个轴突的总长度，这些轴突从耳蜗前腹核(AVCN)的神经元延伸到同侧和对侧的内侧上橄榄核(MSO)。此外，我还将沿着AVCN轴突的不同节段确定轴突直径、髓鞘厚度和兰维尔结节之间的距离。最后，我将测量特定轴突节段的传导速度，并将其与解剖学发现相关联。这些实验将使人们能够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，以在实验上测试调节差异轴突特征对开发符合检测系统的重要性。最终，这项研究将为开发修复听力障碍的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.