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（在噪声中检测语音）和基础神经生物学（计算）原因都非常感兴趣。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。传统上，根据Jeffress在50多年前提出的模型，该电路被认为是延迟线系统的体现，由于其时间上精确的抑制输入，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提供重要的新信息。

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.