Biophysical Specializations Enrich Temporal Selectivity of MSO Neurons

描述(申请人提供)：大脑使用神经细胞和电路属性进行计算，有时根据动作电位的精确时间进行编码和解码。定时在听觉系统中对于各种任务是重要的，例如正确的语音感知，而声音定位的引人注目的例子涉及亚毫秒时间尺度上的时间精度。听觉脑干中的神经元通过检测耳间信号的接近重合来形成声音定位的基础，具有独特的反应特性，例如，在刺激开始时只放电一次。这种跟踪信号快速变化方面的特性掩盖了它们的生物物理构成。它们有一种特殊的钾电流IK-LT，在阈值以下激活，提高了它们的信噪比、锁相能力和检测阈值下信号重合的能力，即使在存在来自听神经自发活动的神经噪声的情况下也是如此。这个项目系统地阐述了脑干神经元的时间处理能力如何依赖于IK-LT和其他生物物理特化(包括其他阈值下的离子电流特征、细胞的树突结构、在胞体-树突膜上哪里是IK-LT的离子通道、快速和精确定时抑制的效果)。随着各种药理制剂被用来选择性地操纵细胞的生物物理成分，时间整合的几个衡量标准被评估。本研究采用实验与理论相结合的研究方法。这些实验包括在体外对单个神经元进行电记录，同时用包括随机成分在内的时变信号直接(或通过汇聚到神经元上的神经束)刺激它们。在理论方面，将开发基于生物物理学的数学模型来模拟和预测神经元的行为。从听觉脑干的这个案例研究中发展出来的概念和见解将被推广到听觉通路中的其他站，并将指导识别奠定时间选择性和神经编码/解码基础的生物物理机制。准确传递与时间相关的线索的能力对于理解语言和听神经病患者的一些缺陷非常重要。因此，这项基础研究直接关系到听力障碍的公共卫生问题。

DESCRIPTION (provided by applicant): The brain performs computations using neuronal cellular and circuit properties, and sometimes encodes and decodes based on the precise timing of action potentials. Timing is important in the auditory system for various tasks, such as proper speech perception and the compelling example of sound localization involves temporal precision on the submillisecond time scale. Neurons in the auditory brain stem that form the basis for sound localization by detecting the near coincidence of interaural signals have distinctive response properties, e.g. firing only once, at stimulus onset. This property of tracking the rapidly changing aspects of a signal belies their biophysical constitution. They have a special potassium current, IK-LT, that activates below threshold, enhancing their signal-to-noise ratio, phase-locking ability and capacity for detecting coincidence of subthreshold signals, even in the presence of neural noise that comes from spontaneous activity in the auditory nerve. This project addresses systematically how the temporal processing ability of a brain stem neuron depends on IK-LT and other biophysical specializations (including other subthreshold ionic current features, the cell's dendritic architecture, where on the soma-dendritic membrane are the ionic channels for IK-LT, the effect of fast and precisely timed inhibition). Several measures of temporal integration are assessed as various pharmacological agents are used to selectively manipulate the cell's biophysical components. The research combines experimental and theoretical approaches. The experiments involve electrical recording from, individaul neurons in vitro while stimulating them directly (or via nerve bundles that converge onto them) with time-varying signals, including random components. From the theoretical side, biophysically based mathematical models will be developed that mimic and predict the neurons' behaviors. The concepts and insights develooped from this case study of auditory brain stem will be extendable to other stations in the auditory pathway and will guide the identification of biophysical mechanisms that underlie temporal selectivity and neural encoding/decoding. The ability to transmit accurately timing-related cues is important for understanding speech and a number of deficits seen in patients with auditory neuropathy. Hence this basic research relates directly to the public health issues of hearing dysfunction.