Nicotinic Modulation of Auditory Cortex Development

听觉皮层发育的烟碱调节

• 批准号: 7058050
• 负责人: KEVIN LIANG
• 金额: $ 3.04万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7058050
• 关键词: auditory cortex; hearing; neurons; nicotine; synapses

DESCRIPTION (provided by applicant): My research will investigate both the functional development of the auditory cortex (ACx), as well as any disruptions posed by early-life chronic nicotine exposure (CNE). Since hearing onset occurs during postnatal development in rats (p12), we can study the physiology of ACx neurons from the first day of hearing in vivo. Therefore, any functional deficiencies in the ACx from developmental nicotine exposure can be monitored in several different manners. First, I plan to record frequency receptive fields from the ACx of young (p13-19) CNE and control rats using both local field potentials and single units (loose-patch). These experiments will determine if CNE impairs frequency tuning in the ACx during an important period for cortical plasticity. Next, I will study how CNE affects synaptic and glutamatergic NMDA receptor maturation in the ACx using both pharmacological and physiological manipulations. Intracortical infusions of NMDAR antagonists (APV and ifenprodil) while recording from the ACx of nicotine treated and control rats will determine the role of NMDARs in receptive field generation. Also, in vivo whole-cell voltage clamp recordings will be conducted to examine how cortical excitation and inhibition develop in both normal and CNE animals, as well as to investigate the existence of pure-NMDAR synapses ("silent synapses") in the developing ACx.

描述（由申请人提供）： 我的研究将调查听觉皮层 (ACx) 的功能发育，以及生命早期慢性尼古丁暴露 (CNE) 造成的任何干扰。由于大鼠的听力开始发生在出生后发育过程中（p12），因此我们可以从体内听力第一天起研究 ACx 神经元的生理学。因此，可以通过几种不同的方式监测因发育期尼古丁暴露而导致的 ACx 功能缺陷。首先，我计划使用局部场电位和单个单元（松散贴片）记录年轻 (p13-19) CNE 和对照大鼠 ACx 的频率感受野。这些实验将确定 CNE 是否会在皮质可塑性的重要时期损害 ACx 的频率调谐。接下来，我将通过药理学和生理学操作研究 CNE 如何影响 ACx 中的突触和谷氨酸 NMDA 受体成熟。皮质内注射 NMDAR 拮抗剂（APV 和艾芬地尔），同时记录尼古丁治疗组和对照大鼠的 ACx，将确定 NMDAR 在感受野生成中的作用。此外，还将进行体内全细胞电压钳记录，以检查正常和 CNE 动物的皮层兴奋和抑制如何发展，并研究发育中的 ACx 中纯 NMDAR 突触（“沉默突触”）的存在。