Silva A J, Stevens C F, Tonegawa S, Wang Y
Howard Hughes Medical Institute, Center for Cancer Research, Cambridge, MA.
Science. 1992 Jul 10;257(5067):201-6. doi: 10.1126/science.1378648.
As a first step in a program to use genetically altered mice in the study of memory mechanisms, mutant mice were produced that do not express the alpha-calcium-calmodulin-dependent kinase II (alpha-CaMKII). The alpha-CaMKII is highly enriched in postsynaptic densities of hippocampus and neocortex and may be involved in the regulation of long-term potentiation (LTP). Such mutant mice exhibited mostly normal behaviors and presented no obvious neuroanatomical defects. Whole cell recordings reveal that postsynaptic mechanisms, including N-methyl-D-aspartate (NMDA) receptor function, are intact. Despite normal postsynaptic mechanisms, these mice are deficient in their ability to produce LTP and are therefore a suitable model for studying the relation between LTP and learning processes.
作为利用基因改造小鼠研究记忆机制计划的第一步，培育出了不表达α-钙调蛋白依赖性蛋白激酶II（α-CaMKII）的突变小鼠。α-CaMKII在海马体和新皮层的突触后致密物中高度富集，可能参与长时程增强（LTP）的调节。此类突变小鼠大多表现出正常行为，且未呈现明显的神经解剖学缺陷。全细胞记录显示，包括N-甲基-D-天冬氨酸（NMDA）受体功能在内的突触后机制是完整的。尽管突触后机制正常，但这些小鼠产生LTP的能力存在缺陷，因此是研究LTP与学习过程之间关系的合适模型。
