Long-term potentiation (LTP) and depression (LTD) at glutamatergic synapses are intensively investigated processes for understanding the synaptic basis for learning and memory, but the underlying molecular mechanisms remain poorly understood. We have made three mouse lines where the C-terminal domains (CTDs) of endogenous AMPA receptors (AMPARs), the principal mediators of fast excitatory synaptic transmission, are specifically exchanged. These mice display profound deficits in synaptic plasticity without any effects on basal synaptic transmission. Our study reveals that the CTDs of GluA1 and GluA2, the key subunits of AMPARs, are necessary and sufficient to drive NMDA receptor-dependent LTP and LTD, respectively. In addition, these domains exert differential effects on spatial and contextual learning and memory. These results establish dominant roles of AMPARs in governing bidirectional synaptic and behavioral plasticity in the CNS.

中文翻译：

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内源性GluA1和GluA2的C末端尾部以不同方式促进海马突触可塑性和学习。

深入研究了谷氨酸能突触的长期增强（LTP）和抑郁（LTD），以了解学习和记忆的突触基础，但对潜在的分子机制仍知之甚少。我们已经制作了三只小鼠系，其中专门交换了内源性AMPA受体（AMPAR）（快速兴奋性突触传递的主要介体）的C末端结构域（CTD）。这些小鼠在突触可塑性上显示出严重的缺陷，对基础突触传递没有任何影响。我们的研究表明，AMPAR关键亚基GluA1和GluA2的CTD分别是驱动NMDA受体依赖性LTP和LTD的必要和充分条件。另外，这些领域对空间和情境学习和记忆产生不同的影响。