Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein
Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein
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DOI：
10.1038/24790
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发表时间：
1998-12-03
期刊：
影响因子：
64.8
通讯作者：
Grant, SGN
中科院分区：
文献类型：
--
作者：
Migaud, M;Charlesworth, P;Grant, SGN
神经元放电的特定模式诱导突触强度的变化，这可能有助于学习和记忆。如果突触后NMDA（N-甲基-D-天冬氨酸）受体被阻断，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被阻止。NMDA受体可以结合称为突触后密度-95（PSD-95）的蛋白质，其可以调节受体的定位和/或信号传导。在缺乏PSD-95的突变小鼠中，NMDA依赖性LTP和LTD的频率函数被移位，以在不同频率的突触刺激下产生显著增强的LTP。与包含双向学习规则的神经网络模型一致，这种频率偏移伴随着严重受损的空间学习。突触NMDA受体电流，亚基表达，定位和突触形态都不受影响的突变小鼠。因此，PSD-95似乎是重要的耦合NMDA受体的途径，控制双向突触可塑性和学习。
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.