Roles of retrograde messengers at inhibitory synapses

1.最近的研究表明，逆行信使可能在中枢神经系统的突触调节和可塑性中发挥重要作用。在海马中，CA1锥体神经元的去极化引起对去极化细胞的抑制性突触输入的瞬时抑制。这种现象被称为DSI（去极化诱导抑制）。海马脑片的研究表明，逆行信使可能参与了DSI。2.本研究以培养的大鼠海马神经元为材料，探讨了DSI的机制以及逆行信使在DSI中的作用。结果和结论如下。(1)A一对培养的海马神经元可以表现出类似于先前报道的海马切片中发生的DSI。（2）细胞外Ca ^2+是DSI诱导的前提条件。（3）抑制电压依赖性Ca ^<2 +>通道可抑制DSI。（4）DSI时突触前末梢抑制性递质的释放受到抑制。（5）蛋白激酶C激活剂（佛波酯）抑制DSI。（6）抑制CaM激酶II可抑制DSI。（7）DSI可以从去极化神经元的突触传递到非去极化神经元的突触。3.这些结果支持了以下关于DSI的假说：突触后神经元去极化通过激活Ca ^2+通道引起突触后细胞内Ca ^2+浓度增加，而Ca ^2+通道又通过依赖于CaM激酶II的过程触发逆行信使的释放。突触前受体的激活逆行信使诱导抑制性传输通过酚酯敏感的过程。

1.Recent studies have suggested that retrograde messengers might play an important role in synaptic modulations and plasticity in the central nervous system. In the hippocampus, depolarization of a CAl pyramidal neuron elicits a transient suppression of inhibitory synaptic inputs to the depolarized cell. This phenomenon is referred to as DSI (depolarization-induced suppression of inhibition). The studies with hippocampal slices demonstrated that a retrograde messenger should be involved in DSI.2.In the present study, we examined mechanisms of DSI and the role of the retrograde messenger in DSI with cultured rat hippocampal neurons. The results and conclusions are as follows.(1)A pair of cultured hippocampal neurons can exhibit DSI similar to that previously reported to occur in hippocampal slices.(2)Extracellular Ca^<2+> ions are prerequisite for the induction of DSI.(3)The inhibition of voltage-dependent Ca^<2+> channels suppresses DSI.(4)The release of the inhibitory transmitter from presynaptic terminals is suppressed during DSI.(5)The protein kinase C activator (phorbol ester) suppresses DSI.(6)The inhibition of CaM kinase II suppresses DSI.(7)DSI can propagate from the synapses on a depolarized neuron to those on a non-depolarized neuron.3.These results support the following hypotheses accounting for DSI.Depolarization of a postsynaptic neuron elicits an increase in postsynaptic intracellular Ca^<2+> concentration by activating Ca^<2+> channels, which in turn triggers the release of retrograde messenger via CaM kinase Il-dependent processes. The activation of presynaptic receptors by the retrograde messenger induces suppression of inhibitory transmission via phobol ester-sensitive processes.