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起重要作用。在海马体中，CAl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短暂抑制。这种现象被称为DSI（去极化诱导抑制）。海马切片研究表明逆行信使参与了dsi。在本研究中，我们研究了培养大鼠海马神经元DSI的机制和逆行信使在DSI中的作用。结果和结论如下：(1)一对培养的海马神经元可以表现出与先前报道的海马切片相似的DSI。(2)胞外Ca^<2+>离子是诱导DSI的先决条件。(3)抑制电压依赖性Ca^<2+>通道抑制DSI。(4) DSI期间突触前末端抑制性递质的释放受到抑制。(5)蛋白激酶C激活剂（磷酸酯）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播到非去极化神经元的突触。这些结果支持以下关于DSI的假设。突触后神经元的去极化通过激活Ca^<2+>通道引起突触后细胞内Ca^<2+>浓度的增加，这反过来通过CaM激酶il依赖性过程触发逆行信使的释放。通过逆行信使激活突触前受体诱导抑制通过phobol酯敏感过程的抑制传递。

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.