Short-term retrograde inhibition of GABAergic synaptic currents in rat Purkinje cells is mediated by endogenous cannabinoids
Short-term retrograde inhibition of GABAergic synaptic currents in rat Purkinje cells is mediated by endogenous cannabinoids
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DOI：
10.1523/jneurosci.22-01-00200.2002
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发表时间：
2002-01-01
影响因子：
5.3
通讯作者：
Marty, A
中科院分区：
文献类型：
--
作者：
Diana, MA;Levenes, C;Marty, A
去极化诱导的抑制抑制（DSI）是GABA能突触传递的一种短期可塑性形式，见于小脑浦肯野细胞和海马CA 1区锥体细胞。DSI涉及由突触后细胞的体树突隔室释放钙依赖性逆行信使。谷氨酸和内源性大麻素都被认为是逆行messager. In这里，我们发现，在小脑旁核切片中，1型大麻素受体（CB 1 Rs）在GABA能中间神经元的轴突和浦肯野细胞的突触前末梢中高水平表达。大麻素拮抗剂AM-251（500 nM）的应用导致在成对记录中记录的诱发电流（eIPSC）的DSI的消除，并且导致从浦肯野细胞记录的TTX不敏感的微型事件（mIPSC）的DSI的强烈降低。此外，CB 1 R激动剂WIN 55- 212，2（5 μ M）诱导突触电流的突触前抑制，类似于在DSI期间发生的突触前抑制，以及刺激浦肯野细胞后DSI的闭塞。此外，WIN 55- 212，2减少了由短列动作电位引起的假定突触前静脉曲张中的钙瞬变，我们的研究结果表明，DSI是由突触前CB 1 Rs的激活介导的，并且内源性大麻素是该制剂中可能的候选逆行信使。他们进一步表明，DSI涉及eIPSC和mIPSC的不同突触前修饰，包括抑制动作电位诱发的钙升高。
Depolarization-induced suppression of inhibition (DSI) is a form of short-term plasticity of GABAergic synaptic transmission that is found in cerebellar Purkinje cells and hippocampal CA1 pyramidal cells. DSI involves the release of a calcium-dependent retrograde messenger by the somatodendritic compartment of the postsynaptic cell. Both glutamate and endogenous cannabinoids have been proposed as retrograde messenger.Here we show that, in cerebellar parasagittal slices, type 1 cannabinoid receptors (CB1Rs) are expressed at high levels in axons of GABAergic interneurons and in presynaptic terminals onto Purkinje cells. Application of the cannabinoid antagonist AM-251 (500 nM) leads to the abolition of the DSI of evoked currents (eIPSCs) recorded in paired recordings and to a strong reduction of the DSI of TTX-insensitive miniature events (mIPSCs) recorded from Purkinje cells. Furthermore, the CB1R agonist WIN 55-212,2 (5 muM) induces a presynaptic inhibition of synaptic currents similar to that occurring during DSI, as well as an occlusion of DSI after stimulation of Purkinje cells. Moreover, WIN 55-212,2 reduces the calcium transients evoked in presumed presynaptic varicosities by short trains of action potentials.Our results indicate that DSI is mediated by the activation of presynaptic CB1Rs and that an endogenous cannabinoid is a likely candidate retrograde messenger in this preparation. They further suggest that DSI involves distinct presynaptic modifications for eIPSCs and mIPSCs, including an inhibition of action potential-evoked calcium rises.