Nicotinic Modulation of Auditory Cortex Development

描述(由申请人提供)： 我的研究将调查听觉皮质(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。由于听力发生在大鼠出生后发育期间(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。因此，可以通过几种不同的方式监测发育中尼古丁暴露引起的ACX的任何功能缺陷。首先，我计划记录年轻(p13-19)CNE和对照组大鼠ACX的频率感受场，既使用局部场电位，也使用单个单位(松散-斑片)。这些实验将确定在皮质可塑性的重要时期，CNE是否会损害ACX的频率调谐。接下来，我将使用药理学和生理学方法研究CNE如何影响ACX中突触和谷氨酸能NMDA受体的成熟。皮质内注射NMDAR拮抗剂(APV和ifenprodil)，同时从尼古丁处理组和对照组大鼠的ACX进行记录，将确定NMDAR在感受野产生中的作用。此外，将进行活体全细胞电压钳记录，以检查正常和CNE动物的皮质兴奋和抑制是如何发展的，以及在发育中的ACX中是否存在纯NMDAR突触(“沉默突触”)。

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.