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Involvements of retrograde signals and glia cells in modulation of synaptic transmissions

逆行信号和神经胶质细胞参与突触传递的调节

基本信息

批准号：
11670036
负责人：
OHNO-SHOSAKU Takako
金额：
$ 2.3万
依托单位：
Kanazawa Uiversity
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
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 CA1 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. To identify the retrograde signal of DSI, we made a paired whole-cell recording from cultured rat hippocampal neurons with inhibitory synaptic connections, and examined the properties of the inhibitory transmission and DSI.In about 60% of pairs, a cannabinoid agonist greatly reduced the release of the inhibitory transmitter GABA from presynaptic terminals. In most of such pairs but not in those insensitive to the agonist, depolarization of postsynaptic neurons and the resultant elevation of intracellular Ca^<2+> concentraton caused transient suppression of inhibitory synaptic currents (DSI), which is mainly due to reduction of GABA release. This DSI was completely blocked by cannabinoid receptor antagonists. The data indicate that endogenous cannabinoids mediate the retrograde signal of DSI.3. These and our previous results support the following hypothesis 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 biosynthesis and release of endogenous cannabinoids. The released cannabinoids bind to presynaptic cannabinoid receptors, and their activation suppresses the transmitter release from inhibitory presynaptic terminals.

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短暂抑制。这种现象被称为DSI（去极化诱导抑制）。海马脑片的研究表明，在DSI中可能有一个逆行信使参与.为了确定DSI的逆行信号，我们从培养的大鼠海马神经元的抑制性突触连接的配对全细胞记录，并检查抑制性传输和DSI的属性。在约60%的对，大麻素激动剂大大减少抑制性递质GABA从突触前末梢的释放。在大多数这样的突触对中，突触后神经元的去极化和由此引起的细胞内Ca^2+浓度的升高引起抑制性突触电流（DSI）的短暂抑制，这主要是由于GABA释放的减少，但对激动剂不敏感的突触对中则不然。大麻素受体拮抗剂可完全阻断DSI。数据表明，内源性大麻素介导的逆行信号的DSI。这些结果和我们以前的研究结果支持了以下解释DSI的假说：突触后神经元的去极化通过激活Ca^2+通道而引起突触后细胞内Ca^2+浓度的增加，这反过来又触发了内源性大麻素的生物合成和释放。释放的大麻素与突触前大麻素受体结合，它们的激活抑制了抑制性突触前末梢的递质释放。