Signaling mechanisms involved in novel synaptic plasticity in excitatory inputs in the cerebellum

2006年，我们发现小脑平行纤维-浦肯野细胞突触的长期增强（LTP）依赖于浦肯野细胞钙水平的升高。由于LTP先前被认为依赖于一氧化氮（NO）信号，LTP被发现同时依赖于Ca^<2+>和NO信号。这些结果还表明Ca^<2+>和NO信号之间可能存在相互作用。因此，在2007年，我们检验了这个假设。一氧化氮供体引起急性小脑浦肯野细胞Ca^<2+>水平升高。PF的爆发性刺激也引起细胞内Ca^<2+>水平升高。pf诱导的Ca^<2+>升高相对缓慢，并被NO合成酶拮抗剂L-NAME完全阻断。这些结果强烈提示，生理状态下浦肯野细胞Ca^<2+>的增加是由no依赖性引起的。此外，还检测了可溶性胍基环化酶（sGC）的参与情况。然而，泡用sGC抑制剂ODQ对浦肯野细胞no依赖性Ca^<2+>升高没有影响。

In 2006, we revealed that long-term potentiation (LTP) of parallel fiber(PF) -Purkinje cell synapse in the cerebellum was dependent on increase in calcium level in Purkinje cells. Because the LTP had been previously indicated to be dependent on nitric oxide (NO) signals, the LTP was revealed to be dependent on both Ca^<2+> and NO signals. These results also suggest possible interaction between Ca^<2+> and NO signals.Thus, in 2007, we examined this hypothesis. Application of NO donor evoked increase in Ca^<2+> levels in Purkinje cells in the acute cerebellar slices. Burst stimulation of PF also induced elevation of intracellular Ca^<2+> levels. The PF-induced Ca^<2+> elevation was relatively slow and completely blocked by L-NAME, an antagonist of NO synthetase. These results strongly indicate that NO-dependent increase in Ca^<2+> in Purkinje cells is evoked in physiological condition. Furthermore, involvement of soluble guanylyl cyclase (sGC) was examined. However, bath application of sGC inhibitor, ODQ, had no effect on the NO-dependent Ca^<2+> increase in Purkinje cells.