Roles of retrograde messengers at inhibitory synapses

逆行信使在抑制性突触中的作用

基本信息

批准号：
09680813
负责人：
OHNO-SHOSAKU Takako
金额：
$ 1.54万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

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.

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。在海马体中，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短暂抑制。这种现象称为 DSI（去极化诱导抑制）。海马切片的研究表明逆行信使应该参与DSI。2.本研究通过培养大鼠海马神经元研究了DSI的机制以及逆行信使在DSI中的作用。结果和结论如下：(1)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)细胞外Ca^2+离子是诱导DSI的先决条件。 (3)电压依赖性Ca^2+通道的抑制抑制DSI。(4)DSI期间突触前末梢释放抑制性递质被抑制。(5)蛋白激酶C激活剂（佛波酯）抑制 DSI。(6)CaM 激酶 II 的抑制抑制 DSI。(7)DSI 可以从去极化神经元上的突触传播到非去极化神经元上的突触。3.这些结果支持以下假设解释 DSI。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，这反过来又通过 CaM 激酶 II 依赖性过程触发逆行信使的释放。逆行信使激活突触前受体，通过佛波醇酯敏感过程诱导抑制性传播的抑制。