LTP requires a reserve pool of glutamate receptors independent of subunit type.

LTP requires a reserve pool of glutamate receptors independent of subunit type.
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DOI:
10.1038/nature11775
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发表时间:
2013-01-24
期刊:
影响因子:
64.8
通讯作者:
--
中科院分区:
综合性期刊1区
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突触传递的长时程增强(LTP)被认为是记忆形成的关键细胞机制。一个被广泛接受的模型假定LTP需要AMPA受体亚基GluA 1的胞质尾区。为了找到GluA 1 C-尾对CA 1海马锥体神经元LTP的最低必要要求,我们使用单细胞分子置换策略用转染的亚基置换所有内源性AMPA受体。与流行的模型形成鲜明对比的是,我们发现LTP不需要GluA 1 C尾。事实上,替换为GluA 2亚单位显示正常的LTP,人工表达的红藻氨酸受体在这些突触中通常不存在。LTP受损的唯一条件是AMPA受体表面表达显著降低,表明需要受体储备库。这些结果表明,突触的显着的灵活性,以加强与各种谷氨酸受体亚型,需要在我们的思想与突触可塑性的核心分子事件的根本变化。
Long-term potentiation (LTP) of synaptic transmission is thought to be a key cellular mechanism underlying memory formation. A widely accepted model posits that LTP requires the cytoplasmic tail of the AMPA receptor subunit GluA1. To find the minimum necessary requirement of the GluA1 C-tail for LTP in CA1 hippocampal pyramidal neurons, we used a single-cell molecular replacement strategy to replace all endogenous AMPA receptors with transfected subunits. In striking contrast to the prevailing model, we found no requirement of the GluA1 C-tail for LTP. In fact, replacement with the GluA2 subunit showed normal LTP, as did an artificially expressed kainate receptor not normally found at these synapses. The only conditions under which LTP was impaired were those with dramatically decreased AMPA receptor surface expression, indicating a requirement for a reserve pool of receptors. These results demonstrate the synapse’s remarkable flexibility to potentiate with a variety of glutamate receptor subtypes, requiring a fundamental change in our thinking with regard to the core molecular events underlying synaptic plasticity.
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