Nicotinic Modulation of Auditory Cortex Development

听觉皮层发育的烟碱调节

• 批准号: 7220610
• 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/7220610
• 关键词: Affect; Age; Amprenavir; Animals; Area; Auditory; Auditory area; Cells; Child; Cholinergic Agents; Chromosome Pairing; Chronic; Cognitive; Control Animal; Development; Disruption; Frequencies; Functional disorder; Generations; Glass; Glutamates; Hearing; Human; In Vitro; Infusion procedures; Laboratories; Lead; Learning Disabilities; Life; Maps; Mediating; Monitor; N-Methyl-D-Aspartate Receptors; Neurons; Nicotine; Physiological; Physiology; Pregnancy; Property; Rattus; Research; Role; Sensory; Staging; Stimulus; Synapses; Testing; Third Pregnancy Trimester; Whole-Cell Recordings; cholinergic; day; ifenprodil; in utero; in vivo; neurodevelopment; postnatal; receptive field; relating to nervous system; research study; response; sensory cortex; voltage clamp

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，以及早期慢性尼古丁暴露（CNE）造成的任何干扰。由于大鼠在出生后发育期间出现听力发作（p12），因此我们可以从体内听力的第一天开始研究ACx神经元的生理学。因此，可以以几种不同的方式监测发育尼古丁暴露引起的ACx的任何功能缺陷。首先，我计划记录频率感受野从ACx的年轻（p13-19）CNE和控制大鼠使用局部场电位和单个单位（松散补丁）。这些实验将确定CNE是否会在皮层可塑性的重要时期损害ACx的频率调谐。接下来，我将研究CNE如何影响突触和NMDA受体成熟的ACx使用药理学和生理操作。皮层内输注NMDAR拮抗剂（APV和艾芬地尔），同时记录尼古丁处理和对照大鼠的ACx，将确定NMDAR在感受野产生中的作用。此外，将进行体内全细胞电压钳记录，以检查皮质兴奋和抑制在正常和CNE动物中如何发展，以及研究发育中的ACx中纯NMDAR突触（“沉默突触”）的存在。