D1 but not D5 dopamine receptors are critical for LTP, spatial learning, and LTP-Induced arc and zif268 expression in the hippocampus
D1 but not D5 dopamine receptors are critical for LTP, spatial learning, and LTP-Induced arc and zif268 expression in the hippocampus
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DOI：
10.1093/cercor/bhm026
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发表时间：
2008-01-01
期刊：
影响因子：
3.7
通讯作者：
Moratalla, Rosario
中科院分区：
文献类型：
--
作者：
Granado, Noelia;Ortiz, Oskar;Moratalla, Rosario
最近的证据表明，多巴胺能和多巴胺能传入必须被激活，以诱导海马中的持续长时程增强（LTP）。虽然大量的证据支持谷氨酸受体在持久的突触可塑性和空间学习和记忆中的作用，但关于多巴胺受体在这些过程中的作用的证据较少。在这里，我们使用多巴胺D-1受体敲除（D1 R-/-）小鼠，以探讨D1 R在海马LTP及其相关基因表达的作用。我们发现，早期和晚期阶段的LTP（E-LTP和L-LTP）的幅度显着减少海马切片从D1 R-/-小鼠与野生型小鼠相比。SCH 23390，一种D-1/D5 R拮抗剂，没有进一步降低D1 R-/-小鼠的L-LTP，表明D（5）R不参与。D1 R-/-小鼠还显示，通过环腺苷3 '，5'-单磷酸活化激活的蛋白激酶，D1 R诱导的N-甲基-D-天冬氨酸介导的电流增强显著降低。最后，在D1 R-/-小鼠中，LTP诱导的海马CA 1区即刻早期基因zif 268和arc的表达被废除，这些小鼠表现出学习受损。这些结果表明，D1 R，而不是D5 R是关键的海马LTP和Zif 268和Arc的诱导，从E-LTP过渡到L-LTP和记忆巩固所需的蛋白质在哺乳动物中。
Recent evidence suggests that glutamatergic and dopaminergic afferents must be activated to induce persistent long-term potentiation (LTP) in the hippocampus. Whereas extensive evidence supports the role of glutamate receptors in long-lasting synaptic plasticity and spatial learning and memory, there is less evidence regarding the role of dopamine receptors in these processes. Here, we used dopamine D-1 receptor knockout (D1R-/-) mice to explore the role of D1R in hippocampal LTP and its associated gene expression. We show that the magnitude of early and late phases of LTP (E-LTP and L-LTP) was markedly reduced in hippocampal slices from D1R-/- mice compared with wild-type mice. SCH23390, a D-1>/D5R antagonist, did not further reduce L-LTP in D1R-/- mice, suggesting that D(5)Rs are not involved. D1R-/- mice also showed a significant reduction of D1R-induced potentiation of N-Methyl-D-aspartic acid-mediated currents, via protein kinase activated by cyclic adenosine 3',5'-monophosphate activation. Finally, LTP-induced expression of the immediate early genes zif268 and arc in the hippocampal CA1 area was abolished in D1R-/- mice, and these mice showed impaired learning. These results indicate that D1R but not D5R are critical for hippocampal LTP and for the induction of Zif268 and Arc, proteins required for the transition from E-LTP to L-LTP and for memory consolidation in mammals.