ENDOGENOUS NITRIC-OXIDE RELEASE REQUIRED FOR LONG-TERM SYNAPTIC DEPRESSION IN THE CEREBELLUM
ENDOGENOUS NITRIC-OXIDE RELEASE REQUIRED FOR LONG-TERM SYNAPTIC DEPRESSION IN THE CEREBELLUM
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DOI：
10.1038/349326a0
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发表时间：
1991-01-24
期刊：
影响因子：
64.8
通讯作者：
OKADA, D
中科院分区：
文献类型：
--
作者：
SHIBUKI, K;OKADA, D
小脑中攀爬纤维和平行纤维的联合刺激会引起平行纤维浦肯野细胞传输的长期抑制 1,2，这种现象与小脑运动学习的细胞机制有关 3。人们怀疑攀爬纤维激活后环 GMP 浓度增加 4 是引起长期抑制的必要条件 3。已知兴奋性氨基酸会导致一氧化氮 (NO) 的释放，从而导致小脑5中cGMP水平升高。在此，我们报道了攀缘纤维刺激后内源性NO释放，平行纤维和攀缘纤维联合刺激引起的长期抑郁被血红蛋白（与NO强烈结合）或L-N（G）-单甲基精氨酸（NO合酶抑制剂）阻断，外源性NO或cGMP可以替代攀爬纤维的刺激引起大鼠长期抑郁小脑切片。 这些结果表明，内源性 NO 的释放对于小脑突触可塑性的诱导至关重要。
CONJUNCTIVE stimulation of climbing and parallel fibres in the cerebellum evokes a long-term depression of parallel-fibre Purkinje-cell transmission 1,2, a phenomenon implicated as the cellular mechanism for cerebellar motor learning 3. It is suspected that the increase in cyclic GMP concentration that occurs after activation of climbing fibres 4 is required to evoke long-term depression 3. Excitatory amino acids are known to cause the release of nitric oxide (NO), resulting in elevation of the cGMP level in the cerebellum 5. Here we report that endogenous NO is released after stimulation of climbing fibres, that long-term depression evoked by conjunctive stimulation of parallel and climbing fibres is blocked by haemoglobin (which strongly binds NO) or L-N(G)-monomethyl-arginine (an inhibitor of NO synthase), and that exogenous NO or cGMP can substitute for the stimulation of climbing fibres to cause long-term depression in rat cerebellar slices. These results demonstrate that the release of endogenous NO is essential for the induction of synaptic plasticity in the cerebellum.