GABAa receptor g[2] knockout: ethanol and spatial memory

GABAa 受体 g[2] 敲除：乙醇和空间记忆

• 批准号: 7118981
• 负责人: DOUGLAS B MATTHEWS
• 金额: $ 6.98万
• 依托单位: UNIVERSITY OF MEMPHIS
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-20 至 2007-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7118981
• 关键词: GABA receptor; alcoholic beverage consumption; alcoholism /alcohol abuse; behavior test; behavioral /social science research tag; diazepam; ethanol; gene expression; gene mutation; genetically modified animals; hippocampus; implant; laboratory mouse; memory; memory disorders; neuropsychology; neurotoxicology; performance; pharmacogenetics; receptor expression; space perception

DESCRIPTION (provided by applicant): Acute ethanol administration impairs spatial memory in both rats and mice. Specifically, ethanol administration impairs the use of spatial memory, spatial learning and blocks spatial contextual learning. Furthermore, the cellular mechanism underlying acute ethanol's impairment of spatial memory has been identified. Namely, acute ethanol administration degrades the spatial specificity of hippocampal place cells recorded in awake freely behaving rats. However, the biochemical mechanism by which acute ethanol administration impairs spatial memory is unknown. Ethanol potentiates GABA-mediated inhibition in a variety of brain regions including brain regions in the hippocampal system. Hence, ethanol might impair spatial memory by potentiating GABA-mediated inhibition in these brain regions thereby altering hippocampal function. However, it is still controversial if ethanol interacts directly with GABAA receptors in brain. The goal of this proposal is to directly investigate if targeted genetic alteration in the gamma2 subunit of the GABAA receptor alters ethanol degradation of spatial memory. GABAA receptor gamma2 heterozygous knockout mice (expressed on the hybrid C57B1/6J - 129/SvJ strain) will be trained a variety of spatial tasks prior to having 1) their spatial memory tested or 2) the spatial specificity of hippocampal place cells determined following administration of one of three doses of ethanol (saline control, 1.25 g/kg, 1.75 g/kg or 2.25 g/kg) or diazepam (1.0 mg/kg, 1.5 mg/kg or 2.0 mg/kg). These studies will directly determine if alterations in GABAA receptor composition via targeted genetic alteration in the gamma2 subunit of the GABAA receptor alter ethanol impairment of spatial memory.

描述（由申请人提供）：急性乙醇给药会损害大鼠和小鼠的空间记忆。具体而言，乙醇给药会损害空间记忆，空间学习并阻止空间上下文学习的使用。 此外，已经确定了急性乙醇对空间记忆的损害的基础机制。也就是说，急性乙醇给药会降低记录在清醒自由行为大鼠中的海马位置细胞的空间特异性。但是，急性乙醇给药损害空间记忆的生化机制尚不清楚。乙醇增强了GABA介导的抑制作用，包括海马系统中的大脑区域。因此，乙醇可能通过增强这些大脑区域的GABA介导的抑制而损害空间记忆，从而改变海马功能。但是，如果乙醇与大脑中的GABAA受体直接相互作用，仍然存在争议。该提案的目的是直接研究GABAA受体γ2亚基的靶向遗传改变是否会改变空间记忆的乙醇降解。 GABAA受体γ2杂合敲除小鼠（在混合C57B1/6J -129/SVJ菌株上表达）将受到各种空间任务的培训g/kg或2.25 g/kg）或地西ep（1.0 mg/kg，1.5 mg/kg或2.0 mg/kg）。这些研究将直接确定GABAA受体组成的改变是否通过GABAA受体的γ2亚基的靶向遗传改变改变了空间记忆的乙醇损害。