Behavioral Measures of Temporal Resolution in Mice With or Without Kv1.1 Subunits

描述（由申请人提供）：所提出的实验的总体目标是检查小鼠在几种听音情况下的听音行为能力。我们将测试在安静的简单声音的检测，单耳时间分辨率敏锐度，双耳声音定位精度。一旦为正常小鼠建立了可靠的行为范例，将对缺乏电压门控钾通道亚基Kv1.1的小鼠采取相同的措施。对这些Kcna 1基因敲除小鼠的体内和体外生理研究表明，这些动物应该具有正常的听觉能力，可以在安静的环境中检测纯音，但时间分辨率较差。这种时间分辨率是否会在单声道和双耳时间处理情况下表现出来是未知的，所以两者都将被测量。尽管比较基因敲除小鼠和野生型小鼠的生理学研究很重要，但它们并没有告诉我们整个清醒的行为动物是如何受到影响的。这里提出的实验将揭示在缺乏完全正常功能的听觉系统的小鼠中可能看到的任何类型的缺陷。这些实验将建立一个可靠的方法来测试小鼠的听觉行为，可用于正常受试者和那些有异常的听觉功能。缺乏基因Kcna 1的小鼠，一种与癫痫、应激诱导的共济失调和人类慢性肌肉抽搐有关的突变，对听觉刺激表现出异常的生理反应。然而，这如何影响这些动物的“真实的世界”听力情况尚不清楚，因此这将在这里确定。

DESCRIPTION (provided by applicant): The overall objective of the proposed experiments is to examine the behavioral abilities of mice to hear in several listening situations. We will test the detection of simple sounds in quiet, the monaural temporal resolution acuity, and binaural sound localization accuracy. Once reliable behavioral paradigms are established for normal mice, these same measures will be taken on mice lacking the voltage-gated potassium channel subunit Kv1.1. Both in vivo and in vitro physiological studies on these Kcna1 knockout mice suggest that these animals should have normal hearing capabilities for detecting pure tones in quiet, but should have poor temporal resolution. Whether this temporal resolution will manifest itself in both monaural and binaural temporal processing situations is unknown, so both will be measured. Although physiological studies comparing knockouts to wild-type mice are important, they do not tell us how the whole, awake, behaving animal is affected. The experiments proposed here will reveal any type of deficit that may be seen in mice lacking a completely normally-functioning auditory system. These experiments will establish a reliable method for testing auditory behavior in mice that can be used for both normal subjects and for those with abnormal auditory functioning. Mice lacking the gene Kcna1, a mutation linked to epilepsy, stress-induced ataxia, and chronic muscle twitching in humans, show abnormal physiological responses to auditory stimuli. It is unknown, however, how this affects the 'real world' listening situation of these animals, so this will be determined here.