Long-lasting synaptic loss after repeated induction of LTD: independence to the means of LTD induction
Long-lasting synaptic loss after repeated induction of LTD: independence to the means of LTD induction
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DOI：
10.1111/j.1460-9568.2006.05032.x
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发表时间：
2006-09-01
影响因子：
3.4
通讯作者：
Ogura, Akihiko
中科院分区：
文献类型：
--
作者：
Kamikubo, Yuji;Egashira, Yoshihiro;Ogura, Akihiko
短期和长期突触可塑性被认为分别是短期和长期记忆的细胞基础。然而，导致持久突触可塑性的细胞后果（假设包括突触形成和消除的过程）仍然未知。使用稳定培养的海马切片，我们之前发现长时程增强（LTP）的重复诱导会引发突触传递强度缓慢发展的持久增强，并伴随突触形成，而突触形成与LTP本身是分开的。我们最近报道了一种明显的镜像效应现象。代谢型谷氨酸受体（mGluR）的反复激活会导致长期抑郁（LTD），引发突触强度的长期降低并伴随着突触消除。为了澄清所报告的持久效应是否特定于之前使用的药物以及该效应是否特定于 mGluR 介导的 LTD，我们将培养的切片反复暴露于另一种 I 组代谢型谷氨酸受体 (mGluR) 激动剂、N-甲基-D-天冬氨酸受体激动剂和 Na+/K+-泵抑制剂。当重复三次时，所有这些治疗均导致同等持久的突触减少/消除，表明重复的 LTD 诱导导致突触消除。突触消除与 LTD 诱导方式的独立性表明，导致短期可塑性和长期可塑性的信号是独立的。对 mGluR 激活代表性案例的详细检查表明，突触强度的降低与突触结构数量的减少相比，延迟了大约 1 周。这种突触消除应该是独特的，因为它依赖于活动而不是不活动。
Short- and long-lasting synaptic plasticity is assumed to be the cellular basis of short- and long-lasting memory, respectively. However, the cellular consequences leading to the long-lasting synaptic plasticity, assumed to include the processes of synapse formation and elimination, remain unknown. Using hippocampal slices maintained stably in culture, we found previously that the repeated induction of long-term potentiation (LTP) triggered a slowly developing long-lasting enhancement in synaptic transmission strength accompanied by synapse formation, which was separate from LTP itself. We recently reported a phenomenon apparently of a mirror-image effect. The repeated activations of metabotropic glutamate receptor (mGluR), which induces long-term depression (LTD), triggered a long-lasting reduction in synaptic strength accompanied by synapse elimination. To clarify whether the reported long-lasting effect was specific to the drugs used previously and whether the effect was specific to mGluR-mediated LTD, we exposed the cultured slices repeatedly to another Group I metabotropic glutamate receptor (mGluR) agonist, an N-methyl-D-aspartate receptor agonist, and a Na+/K+-pump inhibitor. All these treatments resulted in an equivalent long-lasting synaptic reduction/elimination when repeated three times, indicating that the repeated LTD induction leads to synapse elimination. The independence of synapse elimination to the means of LTD induction suggests that the signals leading to short-term plasticity and long-term plasticity are independent. Detailed inspections in the representative case of mGluR activation revealed that the reduction in synaptic strength developed with a similar to 1-week delay from the decrease in the number of synaptic structures. This synapse elimination should be unique as it is activity-dependent rather than inactivity-dependent.