Genetic dissection of LTP/LTD in the hippocampus

描述：(改编自应用程序)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，特别是被广泛研究的长时程增强、长时程增强和长时程抑制现象。在大脑发育完成后，在CA1区诱导基因零突变的技术的发展已经提供了强有力的证据，表明LTP对于空间记忆的发展和海马区CA1区空间的正确表示是必要的。因此，越来越多的证据表明，突触的可塑性是记忆、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，突触可塑性的异常可能在精神分裂症和抑郁症等精神疾病中发挥作用。也有越来越多的实验支持这样的观点，即突触变化是在暴露于滥用和成瘾药物的动物和人类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为在更高水平上探索认知功能和开发针对相关分子靶点的更好的治疗药物提供新的工具。这些实验在很大程度上依赖于麻省理工学院Tonegawa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突变小鼠的行为分析至关重要。Bear(Brown)和Lin(MIT)博士的专业知识和合作对于有效分析突变小鼠的突触可塑性(LTP，LTD)至关重要。

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.