Influences of developmental hearing loss on auditory perception and neural coding

描述（由申请人提供）：许多听觉感知技能在一个令人惊讶的漫长过程中成熟（在人类中），直到青少年时期。如果听力在发育过程中受到干扰，可能会出现听觉感知和语言习得方面的长期缺陷。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；我们所知道的仅仅是基于麻醉动物的录音。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尚不确定的原因。因此，这些研究将首次检查清醒动物的功能发育，并探索编码特性如何受到感觉经验的影响。该建议的中心假设是，发育过程中轻度至中度的传导性HL永久性地破坏了听觉皮层的编码特性，导致知觉表现的可测量缺陷。有三个相关的实验目的。第一目标将确定发育过程中的HL是否会破坏成年动物的感知能力。动物将在一项已知逐渐成熟并受人类听力损失影响的心理物理任务上进行测试：检测正弦振幅调制（SAM）信号的调制深度。第二个目标将描述听觉皮层中神经编码特性的正常发育速率。在目标1中测量的行为感知将与其他同样易受发育干扰的感知一起进行检查。在耳蜗成熟后的发育期间，将在清醒的对照动物中获得单单元记录（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，正如人类行为研究所表明的那样，并寻找SAM检测背后的神经相关性。最后，第三个目的将评估这些编码特性是否以一种与在目的1中测量的电导性HL饲养的动物的感知缺陷相关的方式受到干扰。总之，这些数据将提供对清醒发育动物的听觉编码的首次分析，并揭示HL是否破坏了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意义。通过首先确定中枢听觉系统何时成熟，将有可能确定编码特性是否不能正常发育，或者由于听力损失而提前成熟但开始退化。这一知识对于告知临床医生对早期听力损伤病例进行干预具有重要意义。

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.