Mechanisms of auditory cortex development and role of NMDA receptors

听觉皮层(AC)在复杂声音的处理中起着至关重要的作用。 后天经历的发育变化。早期的听觉体验可以有深刻的 对AC的功能和结构有潜在的持久影响，并影响听力 感知能力和语言能力。先前的研究表明，持续暴露于中等水平的 在关键时间段内没有任何频谱或时间结构的背景噪声延迟 建立交流电的调位图并损害频率选择性，创造交流电发育 延迟(ACDD)。该方案的目的是研究交流发展和噪声产生的机制 ACDD，并揭示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)使用脉冲前抑制(PPI)的声学惊厥反射来评估 在正常发育和ACDD期间的时间分辨率和频率辨别，以及(3)评估 检测正常人群NMDA受体基因和蛋白表达的变化 发展和ACDD。将讨论三个具体目标：(1)AC发生了哪些功能变化 神经元的正常发育和ACDD？(2)时间分辨率和频率如何 辨别力在正常发育和ACDD中的变化？(3)NMDA受体起什么作用 在AC开发和ACDD方面？这项提案中概述的行为实验将是第一个 确定是否有任何与ACDD相关的知觉缺陷。这项研究也将是第一次 探讨NMDA受体在AC正常和异常发育中的作用。这一切的结果是 研究可能会为改善听觉记忆和学习的药物疗法带来新的见解 儿童、失语症患者和人工耳蜗者的缺陷。

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.