Bramham C R, Alkon D L, Lester D S
Laboratory of Adaptive Systems, NINDS, National Institutes of Health, Bethesda, MD 20892.
Neuroscience. 1994 Jun;60(3):737-43. doi: 10.1016/0306-4522(94)90501-0.
In model membranes, arachidonic acid and diacylglycerol have been proposed to synergistically induce a membrane-inserted, constitutively active form of protein kinase C. We have investigated the effects of these lipid protein kinase C activators on synaptic efficacy in the Schaffer collateral input to CA1 hippocampal pyramidal cells. Arachidonic acid (5 microM) perfusion combined with repetitive afferent stimulation had no consistent effect on field excitatory postsynaptic potentials recorded in stratum radiatum, while treatment with a cell-permeable diglyceride, oleoyl-acetylglycerol (5 micrograms/ml), followed by stimulation, led to a short-term potentiation. By contrast, the combination of oleoyl-acetylglycerol and arachidonic acid gave rise to a long-lasting non-decremental potentiation of field excitatory postsynaptic potentials. The induction of potentiation was "activity dependent", as there was either no significant effect or there was a measurable depression when repetitive synaptic stimulation was omitted. Furthermore, consistent with a protein kinase C-dependent process, the potentiation was blocked by the kinase inhibitors H-7 and staurosporine. The results suggest that relatively low concentrations of arachidonic acid and diacylglycerol work synergistically through protein kinase C to persistently enhance synaptic transmission. This synergy has the makings of an associative (Hebbian) device for long-term potentiation induction operating at the second messenger level.
在模型膜中，已有人提出花生四烯酸和二酰基甘油可协同诱导蛋白激酶C形成一种插入膜内的、组成型活性形式。我们研究了这些脂质蛋白激酶C激活剂对海马CA1锥体神经元Schaffer侧支输入突触效能的影响。灌注花生四烯酸（5微摩尔）并结合重复传入刺激，对辐射层记录的场兴奋性突触后电位没有一致的影响，而用细胞可渗透的甘油二酯油酰-乙酰甘油（5微克/毫升）处理后再进行刺激，则会导致短期增强。相比之下，油酰-乙酰甘油和花生四烯酸的组合可引起场兴奋性突触后电位的持久非递减增强。增强的诱导是“活动依赖性的”，因为当省略重复突触刺激时，要么没有显著影响，要么有可测量的抑制。此外，与蛋白激酶C依赖性过程一致，增强被激酶抑制剂H-7和星形孢菌素阻断。结果表明，相对低浓度的花生四烯酸和二酰基甘油通过蛋白激酶C协同作用，持续增强突触传递。这种协同作用具有在第二信使水平上进行长期增强诱导的联合（赫布）装置的特征。
