Long-term depression in rat cerebellum requires both NO synthase and NO-sensitive guanylyl cyclase
Long-term depression in rat cerebellum requires both NO synthase and NO-sensitive guanylyl cyclase
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DOI：
10.1111/j.1460-9568.1996.tb00743.x
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发表时间：
1996-10-01
影响因子：
3.4
通讯作者：
Garthwaite, J
中科院分区：
文献类型：
--
作者：
Boxall, AR;Garthwaite, J
平行纤维和浦肯野细胞之间突触传递的长期抑制（LTD）是发生在小脑中的突触可塑性的一个众所周知的例子。一氧化氮（NO）与大脑其他区域的突触可塑性有关，但其在小脑LTD中的功能存在争议。即使提示有参与，NO信号转导通路也不清楚。一种候选物质是环gmp合成酶，即可溶性胍基环化酶，其在大脑和其他部位的活性受到NO的强烈刺激。通过记录小脑浦肯野细胞的细胞内切片，我们证明NO合酶的阻断完全抑制平行纤维刺激与突触后Ca2+尖峰放电诱导的LTD。细胞内应用1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one也能阻断LTD，这是一种最近发现的可溶性guanyyl环化酶的有效选择性抑制剂。这些发现表明，小脑有限责任公司需要可溶性关酰环化酶，并表明这种酶位于浦肯野细胞内，以这种突触可塑性的形式转导NO信号。
Long-term depression (LTD) of synaptic transmission between parallel fibres and Purkinje cells is a well-known example of synaptic plasticity taking place in the cerebellum. Nitric oxide (NO) has been implicated in synaptic plasticity in other brain areas, but its function in cerebellar LTD is controversial. Even when an involvement is suggested, the NO signal transduction pathway is unclear. One candidate is the cyclic GMP-synthesizing enzyme, soluble guanylyl cyclase, whose activity in the brain and elsewhere is powerfully stimulated by NO. By recording intracellularly from Purkinje cells in cerebellar slices, we demonstrate that blockade of NO synthase completely inhibits LTD induced by pairing parallel fibre stimulation with postsynaptic Ca2+ spike firing. LTD was also blocked by intracellular application of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a recently identified potent and selective inhibitor of soluble guanylyl cyclase. These findings indicate that soluble guanylyl cyclase is required for cerebellar LTD and suggest that this enzyme, located within Purkinje cells, transduces the NO signal in this form of synaptic plasticity.