Mechanisms of auditory cortex development and role of NMDA receptors

听觉皮层（AC）在处理复杂声音中起着关键作用， 由于出生后经历而产生的发育变化。早期的听觉体验会给我们 对AC的功能和结构产生潜在的长期影响，并影响听力 感知和语言能力。以前的研究表明，持续暴露于中等水平的 在临界周期期间没有任何频谱或时间结构的背景噪声延迟了 建立AC的音调分布图，损害频率选择性， 延迟（ACDD）。本研究的目的是研究交流的发展和噪声诱导的机制 探讨NMDA受体在AC发生和ACDD中的作用。为了实现这一目标，我 将（1）使用长期植入的电极来监测AC中神经元的反应特性， 正常发育和ACDD，（2）使用声惊吓反射的前脉冲抑制（PPI）来评估 正常发育和ACDD期间时间分辨率和频率辨别力，以及（3）评估 通过测定mRNA和蛋白质水平，观察正常大鼠脑组织中NMDA受体表达的变化。 发展和ACDD。本研究的目的有三：（1）AC发生了什么样的功能变化 神经元在正常发育和ACDD？(2)时间分辨率和频率 歧视的变化，在正常的发展和ACDD？(3)NMDA受体在其中扮演什么角色 在AC开发和ACDD？本提案中概述的行为实验将首次 确定是否存在与ACDD相关的任何感知缺陷。这项研究也将是第一个 评价NMDA受体在正常和异常AC发育中的作用。这些的结果 这些研究可能会对改善听觉记忆和学习的药物疗法产生新的见解 儿童、失语症患者和人工耳蜗使用者的缺陷。

The auditory cortex (AC) which plays a crucial role in processing complex sounds undergoes significant developmental changes as a result of postnatal experience. Early auditory experience can have a profound and potentially long lasting effect on the function and structure of the AC, and influence the hearing perception and language ability. Previous studies suggest that continuous exposure to moderate-level background noise without any spectral or temporal structure during the critical period delays the establishment of the tonotopic map of the AC and impairs frequency selectivity, creating AC developmental delay (ACDD). The goal of this proposal is to study the mechanism of AC development and noise induced ACDD, and to reveal the role of NMDA receptors in AC development and ACDD. To accomplish this goal, I will (1) use chronically implanted electrodes to monitor the response properties of neurons in AC during normal development and ACDD, (2) use pre-pulse inhibition (PPI) of the acoustic startle reflex to assess temporal resolution and frequency discrimination during normal development and ACDD, and (3) evaluate the change in NMDA receptor expression by measuring mRNA and protein levels during normal development and ACDD. Three specific aims will be addressed: (1) what functional changes occuring in AC neuron during the normal development and ACDD? (2) How does the temporal resolution and frequency discrimination change during the normal development and in ACDD? (3) what role do NMDA receptors play in AC development and ACDD? The behavioral experiments outlined in this proposal will be the first to determine if there are any perceptual deficits associated with the ACDD. The research will also be the first to evaluate the role of NMDA receptors in normal and abnormal AC development. The result of these studies may lead to new insights into pharmacologic therapies for improving auditory memory and learning deficits in children, aphasia patients and cochlear implant users.