Migaud M, Charlesworth P, Dempster M, Webster L C, Watabe A M, Makhinson M, He Y, Ramsay M F, Morris R G, Morrison J H, O'Dell T J, Grant S G
Centre for Genome Research, University of Edinburgh, UK.
Nature. 1998 Dec 3;396(6710):433-9. doi: 10.1038/24790.
Specific patterns of neuronal firing induce changes in synaptic strength that may contribute to learning and memory. If the postsynaptic NMDA (N-methyl-D-aspartate) receptors are blocked, long-term potentiation (LTP) and long-term depression (LTD) of synaptic transmission and the learning of spatial information are prevented. The NMDA receptor can bind a protein known as postsynaptic density-95 (PSD-95), which may regulate the localization of and/or signalling by the receptor. In mutant mice lacking PSD-95, the frequency function of NMDA-dependent LTP and LTD is shifted to produce strikingly enhanced LTP at different frequencies of synaptic stimulation. In keeping with neural-network models that incorporate bidirectional learning rules, this frequency shift is accompanied by severely impaired spatial learning. Synaptic NMDA-receptor currents, subunit expression, localization and synaptic morphology are all unaffected in the mutant mice. PSD-95 thus appears to be important in coupling the NMDA receptor to pathways that control bidirectional synaptic plasticity and learning.
特定的神经元放电模式会引起突触强度的变化，这可能有助于学习和记忆。如果阻断突触后N-甲基-D-天冬氨酸（NMDA）受体，突触传递的长时程增强（LTP）和长时程抑制（LTD）以及空间信息的学习就会受到阻碍。NMDA受体可以结合一种名为突触后致密蛋白95（PSD-95）的蛋白质，该蛋白质可能调节受体的定位和/或信号传导。在缺乏PSD-95的突变小鼠中，NMDA依赖性LTP和LTD的频率功能发生改变，在不同频率的突触刺激下产生显著增强的LTP。与纳入双向学习规则的神经网络模型一致，这种频率变化伴随着严重受损的空间学习能力。突变小鼠的突触NMDA受体电流、亚基表达、定位和突触形态均未受影响。因此，PSD-95似乎在将NMDA受体与控制双向突触可塑性和学习的通路耦合方面起着重要作用。
