Li Y, Erzurumlu R S, Chen C, Jhaveri S, Tonegawa S
Howard Hughes Medical Institute, Center for Cancer Research, Cambridge, Massachusetts.
Cell. 1994 Feb 11;76(3):427-37. doi: 10.1016/0092-8674(94)90108-2.
Sensory pathways of the brain generally develop from crudely wired networks to precisely organized systems. Several studies have implicated neural activity-dependent mechanisms, including N-methyl-D-aspartate (NMDA) receptors, in this refinement process. We applied the gene targeting to the NMDAR1 gene and created a mutant mouse that lacks functional NMDA receptors. The development of whisker-related patterns in the trigeminal nuclei of the mutant mice and their normal littermates was compared. We show that in the mutant mice pathfinding, initial targeting, and crude topographic projection of trigeminal axons in the brainstem are unaffected, but that whisker-specific patches fail to form. Our results provide a direct demonstration of the involvement of the NMDA receptor in the formation of periphery-related neural patterns in the mammalian brain.
大脑的感觉通路通常从粗略连接的网络发展为精确组织的系统。几项研究表明,在这个细化过程中涉及神经活动依赖机制,包括N-甲基-D-天冬氨酸(NMDA)受体。我们将基因靶向应用于NMDAR1基因,创建了一种缺乏功能性NMDA受体的突变小鼠。比较了突变小鼠及其正常同窝小鼠三叉神经核中与触须相关模式的发育情况。我们发现,在突变小鼠中,脑干中三叉神经轴突的路径寻找、初始靶向和粗略的拓扑投射不受影响,但触须特异性斑块未能形成。我们的结果直接证明了NMDA受体参与了哺乳动物大脑中与外周相关神经模式的形成。