MOLECULAR REGULATION OF GABAA RECEPTORS IN THE AMYGDALA

杏仁核中 GABAA 受体的分子调控

• 批准号: 8172380
• 负责人: KERRY J. RESSLER
• 金额: $ 3.29万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172380
• 关键词: Acute; Amnesia; Amygdaloid structure; Animals; Anticonvulsants; Behavioral; Chronic; Computer Retrieval of Information on Scientific Projects Database; Data; Detection; Dose; Fright; Funding; Grant; In Vitro; Institution; Knockout Mice; Lentivirus Vector; Locomotion; Mediating; Molecular; Motor; Proteins; Regulation; Reporting; Research; Research Personnel; Resources; Sedation procedure; Seizures; Source; Subfamily lentivirinae; United States National Institutes of Health; Withdrawal; Work; cohort; drug testing; gephyrin; in vivo; receptor; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We made considerable progress during the reporting period. We completed all of the fear-related aspects and obtained pilot data on the acute, chronic, and withdrawal of BZD treatment. We examined the effects of the various levels of test drugs on motor locomotion (sedation), PTz-induced seizures (anticonvulsant effects), and the acquisition of Pavlovian contextual fear (amnesia) in separate cohorts of animals. We determined what PTZ dose level (25-100 mg/kg) produced seizures both reliably and at levels which allowed detection of experimentally-induced changes. We worked to maximize our ability to silence the Gephyrin protein in vitro and in vivo with lentiviral vectors. We continued to work with the knockout mouse line, and worked to "rescue" GAD65 with lentivirus-mediated GAD65 expression. We completed work on a lentiviral vector that convincingly decreases GAD67 expression, and began using this tool for behavioral studies.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在本报告所述期间，我们取得了相当大的进展。我们完成了所有与恐惧相关的方面，并获得了关于BZD急性、慢性和停药治疗的试点数据。我们在不同的动物队列中检测了不同水平的测试药物对运动(镇静)、PTZ诱导的癫痫(抗惊厥效果)和巴甫洛夫情景恐惧(健忘症)获得的影响。 我们确定了什么PTZ剂量水平(25-100 mg/kg)会可靠地产生癫痫发作，并在允许检测到实验诱导的变化的水平上进行。我们致力于通过慢病毒载体最大限度地提高我们在体外和体内沉默吉普林蛋白的能力。 我们继续研究基因敲除的小鼠品系，并致力于用慢病毒介导的GAD65表达来“拯救”GAD65。我们完成了一种能够令人信服地降低GAD67表达的慢病毒载体的工作，并开始将该工具用于行为研究。