Department of Neurophysiology, Graduate School of Medicine, University of Tokyo, Tokyo 113-0033, Japan.
Neuron. 2010 Feb 11;65(3):320-7. doi: 10.1016/j.neuron.2010.01.021.
Endocannabinoids are released from postsynaptic neurons and cause retrograde suppression of synaptic transmission. Anandamide and 2-arachidonoylglycerol (2-AG) are regarded as two major endocannabinoids. To determine to what extent 2-AG contributes to retrograde signaling, we generated and analyzed mutant mice lacking either of the two 2-AG synthesizing enzymes diacylglycerol lipase alpha (DGLalpha) and beta (DGLbeta). We found that endocannabinoid-mediated retrograde synaptic suppression was totally absent in the cerebellum, hippocampus, and striatum of DGLalpha knockout mice, whereas the retrograde suppression was intact in DGLbeta knockout brains. The basal 2-AG content was markedly reduced and stimulus-induced elevation of 2-AG was absent in DGLalpha knockout brains, whereas the 2-AG content was normal in DGLbeta knockout brains. Morphology of the brain and expression of molecules required for 2-AG production other than DGLs were normal in the two knockout mice. We conclude that 2-AG produced by DGLalpha, but not by DGLbeta, mediates retrograde suppression at central synapses.
内源性大麻素从突触后神经元释放，并导致突触传递的逆行抑制。大麻素和 2-花生四烯酸甘油（2-AG）被认为是两种主要的内源性大麻素。为了确定 2-AG 在逆行信号传递中起到多大作用，我们生成并分析了两种 2-AG 合成酶二酰基甘油脂肪酶 α（DGLalpha）和β（DGLbeta）缺失的突变体小鼠。我们发现，DGLalpha 敲除小鼠的小脑、海马和纹状体中完全不存在内源性大麻素介导的逆行突触抑制，而 DGLbeta 敲除小鼠的逆行抑制则完整。DGLalpha 敲除小鼠的基础 2-AG 含量明显降低，刺激诱导的 2-AG 升高也不存在，而 DGLbeta 敲除小鼠的 2-AG 含量正常。在这两种敲除小鼠中，大脑的形态和除 DGL 以外的 2-AG 产生所需的分子的表达都是正常的。我们得出结论，DGLalpha 产生的 2-AG 介导了中枢突触的逆行抑制，但 DGLbeta 产生的 2-AG 则没有。
