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

描述（由申请人提供）：拟议实验的总体目标是检查小鼠在几种听力情况下的听力行为能力。我们将测试在安静环境下对简单声音的检测，单耳时间分辨率的灵敏度，双耳声音定位的精度。一旦在正常小鼠身上建立了可靠的行为范式，将在缺乏电压门控钾通道亚基Kv1.1的小鼠身上采取相同的措施。对这些Kcna1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力能力，可以在安静环境下检测纯音，但时间分辨率应该较差。这种时间分辨率是否会在单耳和双耳时间加工情况下表现出来是未知的，所以这两种情况都将被测量。尽管将基因敲除小鼠与野生型小鼠进行比较的生理学研究很重要，但它们并没有告诉我们，整个清醒、行为正常的小鼠是如何受到影响的。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。这些实验将建立一种可靠的方法来测试小鼠的听觉行为，这种方法既可以用于正常受试者，也可以用于听觉功能异常的受试者。缺乏Kcna1基因的小鼠对听觉刺激表现出异常的生理反应。Kcna1基因是一种与癫痫、应激性共济失调和人类慢性肌肉抽搐有关的突变。然而，目前尚不清楚这如何影响这些动物在“现实世界”的听力状况，所以这将在这里确定。

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.