Biophysical Specializations Enrich Temporal Selectivity of MSO Neurons

描述（由申请人提供）：大脑使用神经元细胞和电路特性进行计算，有时基于动作电位的精确定时进行编码和解码。在听觉系统中，时间对于各种任务都很重要，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而形成声音定位的基础，这些神经元具有独特的响应特性，例如在刺激开始时仅发射一次。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，增强它们的信噪比，锁相能力和检测阈下信号重合的能力，即使在存在来自听觉神经自发活动的神经噪声的情况下。该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和其他生物物理学特化（包括其他阈下离子电流特征，细胞的树突结构，在胞体-树突膜上的IK-LT离子通道，快速和精确定时抑制的效果）。时间整合的几个措施进行评估，因为各种药物被用来选择性地操纵细胞的生物物理成分。本研究采用实验和理论相结合的方法。这些实验涉及在体外对单个神经元进行电记录，同时用时变信号（包括随机分量）直接刺激它们（或通过会聚到它们上的神经束）。从理论上讲，将开发基于生物药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扩展到听觉通路中的其他站点，并将指导识别时间选择性和神经编码/解码的生物物理机制。准确传递时间相关线索的能力对于理解语音和听神经病患者中出现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.