Mechanisms of auditory cortex development and role of NMDA receptors

听觉皮层发育机制和 NMDA 受体的作用

• 批准号: 7324815
• 负责人: WEI SUN
• 金额: $ 7.93万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7324815
• 关键词: ARHGEF5 gene; Acoustics; Address; Adult; Affect; Animal Model; Animals; Aphasia; Auditory; Auditory Perception; Auditory area; Auditory system; Behavioral; Brain; Child; Chronic; Cochlear Implants; Complex; Data; Development; Developmental Delay Disorders; Discrimination; Electrodes; Environment; Exposure to; Frequencies; Goals; Hearing; Hearing Impaired Persons; Housing; Implant; Implanted Electrodes; Language; Language Development; Lead; Learning; Life; Long-Term Potentiation; Maps; Measures; Memory; Messenger RNA; Monitor; N-Methyl-D-Aspartate Receptors; Neurons; Newborn Infant; Noise; Normal Range; Patients; Physiologic pulse; Play; Process; Property; Proteins; Pulse taking; Rattus; Reflex action; Rehabilitation therapy; Reporting; Research; Resolution; Role; Signal Transduction; Speech; Structure; Techniques; Training; base; behavior measurement; critical developmental period; experience; improved; insight; language training; postnatal; receptor expression; receptor function; research study; response; sound; success

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.

在处理复杂声音中起重要作用的听觉皮层（AC）具有重要的作用 由于产后经验而变化。早期的听觉经验可以具有深刻的 并可能对AC的功能和结构产生持久的持久影响，并影响听力 感知和语言能力。先前的研究表明，连续暴露于中等水平 在关键时期内没有任何光谱或时间结构的背景噪声延迟 建立AC的吨位图并损害频率选择性，创造AC发育 延迟（ACDD）。该提案的目的是研究AC发育和噪声引起的机制 ACDD，并揭示NMDA受体在AC发育和ACDD中的作用。为了实现这一目标，我 （1）使用慢性植入电极监测AC中神经元的反应特性 正常发育和ACDD，（2）使用声学惊吓反射的前脉冲抑制（PPI）来评估 正常发育和ACDD期间的时间分辨率和频率歧视，（3）评估 NMDA受体表达的变化通过测量正常情况下的mRNA和蛋白质水平 开发和ACDD。将解决三个具体目标：（1）AC中发生什么功能变化 正常发育和ACDD期间的神经元？ （2）时间分辨率和频率如何 在正常发展和ACDD中的歧视变化？ （3）NMDA受体扮演什么角色 在AC开发和ACDD中？该提案中概述的行为实验将是第一个 确定是否存在与ACDD相关的任何知觉缺陷。这项研究也将是第一个 评估NMDA受体在正常和异常AC发育中的作用。这些结果 研究可能会导致对改善听觉记忆和学习的药理疗法的新见解 儿童，失语症患者和人工耳蜗使用者的缺陷。