Department of Physiology, Hyogo College of Medicine, Nishinomiya 663-8501, Japan.
Neuroscience. 2010 Dec 29;171(4):973-80. doi: 10.1016/j.neuroscience.2010.10.021. Epub 2010 Oct 13.
Although the hippocampus is a brain region involved in short-term memory, the molecular mechanisms underlying memory formation are not completely understood. Here we show that sphingosine 1-phosphate (S1P) plays a pivotal role in the formation of memory. Addition of S1P to rat hippocampal slices increased the rate of AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) recorded from the CA3 region of the hippocampus. In addition long-term potentiation (LTP) observed in the CA3 region was potently inhibited by a sphingosine kinase (SphK) inhibitor and this inhibition was fully reversed by S1P. LTP was impaired in hippocampal slices specifically in the CA3 region obtained from SphK1-knockout mice, which correlates well with the poor performance of these animals in the Morris water maze test. These results strongly suggest that SphK/S1P receptor signaling plays an important role in excitatory synaptic transmission in the CA3 region of hippocampus and has profound effects on hippocampal function such as spatial learning.
虽然海马体是一个与短期记忆相关的脑区，但记忆形成的分子机制仍不完全清楚。在这里，我们发现鞘氨醇 1-磷酸（S1P）在记忆形成中起着关键作用。向大鼠海马切片中添加 S1P 可增加从海马 CA3 区记录到的 AMPA 受体介导的微小兴奋性突触后电流（mEPSC）的速率。此外，SphK 抑制剂强烈抑制 CA3 区的长时程增强（LTP），而 S1P 可完全逆转这种抑制。SphK1 基因敲除小鼠的海马切片中 LTP 受损，特别是在 CA3 区，这与这些动物在 Morris 水迷宫测试中的表现不佳密切相关。这些结果强烈表明 SphK/S1P 受体信号在海马 CA3 区的兴奋性突触传递中起着重要作用，并对海马功能（如空间学习）产生深远影响。
