Genetic dissection of LTP/LTD in the hippocampus

海马 LTP/LTD 的基因剖析

• 批准号: 6346267
• 负责人: STEPHEN FOX HEINEMANN
• 金额: $ 17.02万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6346267
• 关键词: AMPA receptors; NMDA receptors; calcium flux; electrophysiology; gene targeting; genetically modified animals; glutamate receptor; hippocampus; laboratory mouse; long term potentiation; memory; neural information processing; neural plasticity; synapses

DESCRIPTION: (Adapted from Application) We will use a genetic approach to test a number of popular ideas about the mechanisms of synaptic plasticity, specifically the well-studied phenomenon of long term potentiation, LTP, and long term depression, LTD. The development of technology to induce null mutations in genes specifically in the CAI region and after completion of brain development has provided strong evidence that LTP is necessary for the development of spatial memory and a proper representation of space in the CA1 region of the hippocampus. Thus, there is mounting evidence that synaptic plasticity underlies memory and learning and other cognitive functions. Synaptic plasticity is likely to play an important role in the proper development of the brain and it is possible that aberrations in synaptic plasticity play a role in mental illnesses such as schizophrenia and depression. There is also growing experimental support for the idea that synaptic alterations underlie the long-term changes in brain function observed in animals and humans exposed to drugs of abuse and addiction. Understanding the mechanisms of synaptic plasticity at the detailed molecular level will lead to new tools to explore cognitive function at a higher level and to the development of better therapeutic drugs directed to relevant molecular targets. The experiments depend critically on mutant mice and genetic engineering technology generated at MIT in the Tonegawa laboratory. The new multiple recording methods developed in the Wilson laboratory at MIT are essential for the behavioral analysis of the mutant mice. The expertise and collaboration of Drs. Bear (Brown) and Lin (MIT) are vital for the efficient analysis of synaptic plasticity (LTP, LTD) in the mutant mice.

产品说明：（改编自应用）我们将使用遗传学方法来测试一些关于突触可塑性机制的流行观点，特别是研究充分的长时程增强现象，LTP和长时程抑制，技术的发展，以诱导无效突变的基因，特别是在CAI区和完成后的大脑发育提供了强有力的证据，LTP是必要的发展空间记忆和海马体CA1区空间的正确表征。因此，越来越多的证据表明，突触可塑性是记忆、学习和其他认知功能的基础。突触可塑性可能在大脑的正常发育中发挥重要作用，突触可塑性的畸变可能在精神疾病如精神分裂症和抑郁症中发挥作用。越来越多的实验支持这样一种观点，即突触改变是在动物和人类暴露于滥用和成瘾药物中观察到的大脑功能长期变化的基础。在详细的分子水平上了解突触可塑性的机制将导致新的工具，以探索认知功能在更高的水平和更好的治疗药物的发展，针对相关的分子靶点。这些实验主要依赖于麻省理工学院利根川实验室的突变小鼠和基因工程技术。麻省理工学院威尔逊实验室开发的新的多重记录方法对于突变小鼠的行为分析至关重要。Bear博士（Brown）和Lin博士（MIT）的专业知识和合作对于突变小鼠中突触可塑性（LTP，LTD）的有效分析至关重要。