Influences of developmental hearing loss on auditory perception and neural coding

描述（由申请人提供）：许多听觉感知技能的成熟经历了一个令人惊讶的长时间过程（在人类中），直到十几岁。如果听力在发育过程中受到干扰，听觉感知和语言习得可能会出现长期缺陷。令人惊讶的是，支持这些新兴感知技能的听觉编码特性的成熟在很大程度上是未知的;我们所知道的很少是完全基于麻醉动物的记录。这也是为什么我们对听力损失（HL）对中枢听觉成熟的影响的理解是不确定的。因此，这些研究将首次研究清醒动物的功能发育，并探索编码特性如何受到感官体验的影响。这个建议的中心假设是，轻度至中度的导电HL在发展过程中永久性地破坏编码特性的听觉皮层，导致可测量的赤字的知觉表现。有三个相关的实验目标。第一个目标是确定HL在发育过程中是否会破坏成年动物的感知能力。将对动物进行心理物理任务测试，该任务已知逐渐成熟并受到人类听力损失的影响：检测正弦幅度调制（SAM）信号中的调制深度。第二个目标将描述听觉皮层神经编码特性的正常发育速率。目标1中的行为感知将与其他同样易受发展扰动影响的感知一起进行沿着检查。在耳蜗成熟后的发育期间，将在清醒对照动物中获得单个单位记录（因此，将不评估外周处理）。广泛的目标是确定编码特性是否以不同的速度成熟，如人类行为研究所建议的那样，并寻找SAM检测的神经相关性。最后，第三个目标将评估这些编码特性是否以与目标1中测量的用传导性HL饲养的动物的感知缺陷相关的方式受到干扰。总之，这些数据将提供清醒发育动物听觉编码的第一次分析，并揭示HL是否会破坏感知技能和支持它们的编码特性。这些研究具有直接的临床相关性。通过首先确定中枢听觉系统何时达到成熟，将有可能确定编码特性是否未能正常发展，或者是否较早达到成熟但由于听力损失而开始退化。这方面的知识将是重要的通知临床医生干预的情况下，早期听力障碍。

Description (provided by applicant): Many auditory perceptual skills mature over a surprisingly long time course (in humans), well into the teenage years. If hearing is disrupted during development, there may be long-lasting deficits in auditory perception and language acquisition. Surprisingly, maturation of the auditory coding properties that support these emerging perceptual skills are largely unknown; what little we do know is based solely on recordings from anesthetized animals. This is also why our understanding of the effect of hearing loss (HL) on central auditory maturation is unsettled. These studies will thus examine functional development in awake animals for the first time, and explore how coding properties are influenced by sensory experience. The central hypothesis of this proposal is that mild to moderate conductive HL during development permanently disrupts coding properties in the auditory cortex, leading to measurable deficits in perceptual performance. There are three related experimental aims. The FIRST AIM will determine whether HL during development disrupts the perceptual abilities of adult animals. Animals will be tested on a psychophysical task known to mature gradually and to be affected by hearing loss in humans: detection of modulation depth in sinusoidally amplitude modulated (SAM) signals. The SECOND AIM will characterize the normal rate of development of neural coding properties in auditory cortex. Those percepts measured behaviorally in Aim 1 will be examined along with other percepts similarly susceptible to developmental perturbation. Single unit recordings will be obtained in awake control animals during the period of development that follows maturation of the cochlea (thus, peripheral processing will not be assessed). The broad goals are to determine whether coding properties mature at different rates, as suggested by human behavioral studies, and to search for neural correlates underlying SAM detection. Finally, the THIRD AIM will assess whether these coding properties are perturbed in a manner that correlates with perceptual deficits in animals reared with conductive HL, measured in Aim 1. Together, these data will provide the first analysis of auditory coding in awake developing animals, and reveal whether HL disrupts both perceptual skills and the coding properties that support them. These studies have direct clinical relevance. By first determining when the central auditory system reaches maturity, it will be possible to determine whether coding properties fail to develop normally, or reach maturity early but begin to regress due to hearing loss. This knowledge will be important in informing clinicians for intervention in cases of early hearing impairment.