MOLECULAR DISSECTION OF GLUTAMATE RECEPTORS

谷氨酸受体的分子解剖

• 批准号: 2891541
• 负责人: DAVID E FEATHERSTONE
• 金额: $ 3.67万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-06-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2891541
• 关键词: Caenorhabditis elegans; animal genetic material tag; avoidance behavior; behavioral /social science research tag; ethology; excitatory aminoacid; gene deletion mutation; glutamate receptor; neural transmission; neurons; neuropharmacology; osmotic pressure; protein structure function; psychomotor function

Glutamate is the primary excitatory neurotransmitter in the mammalian brain. Many important neural functions (including synaptic response duration, learning and memory) are thought to be dependent on specific subunit-conferred glutamate receptor properties. Changes in glutamate receptor function have also been implicated in many abnormal phenomena, such as epilepsy, schizophrenia, Alzheimer's and Huntington's diseases, neurodegenerative diseases, and excitotoxicity secondary to stroke. The broad aim of this proposal is to study how subunit composition determines glutamate receptor function and neural behavior, using the model organism C. elegans. Specifically, this proposed work will: 1) develop electrophysiological methods for reliably recording glutamate responses from identified neurons in C. elegans. 2) Characterize the glutamate response of an identified neuron in both wildtype animals and in mutants in which each glutamate receptor subunit has been deleted, and 3) Characterize behaviors mediated by the identified neuron in both wildtype and mutant animals. This project will build on the trainee's electrophysiology experience and introduce him to molecular biology and genetics while developing a powerful new model system for future work in molecular neurobiology.

谷氨酸是哺乳动物中主要的兴奋性神经递质 脑。 许多重要的神经功能（包括突触反应 持续时间、学习和记忆）被认为取决于特定的 亚基赋予的谷氨酸受体特性。 谷氨酸的变化 受体功能也与许多异常现象有关， 例如癫痫症、精神分裂症、阿尔茨海默病和亨廷顿舞蹈病， 神经退行性疾病和中风继发的兴奋性毒性。 该提案的主要目标是研究亚基组成如何 确定谷氨酸受体功能和神经行为，使用 模型生物线虫。 具体来说，这项拟议的工作将：1) 开发可靠记录谷氨酸的电生理学方法 线虫中已识别神经元的反应。 2）表征 野生型动物和已鉴定神经元的谷氨酸反应 在每个谷氨酸受体亚基都被删除的突变体中， 3）表征由所识别的神经元介导的行为 野生型和突变型动物。 该项目将建立在学员的电生理学经验的基础上 并向他介绍分子生物学和遗传学，同时开发 为分子神经生物学的未来工作提供强大的新模型系统。