Boxall A R, Garthwaite J
Cruciform Project, University College London, UK.
Eur J Neurosci. 1996 Oct;8(10):2209-12. doi: 10.1111/j.1460-9568.1996.tb00743.x.
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.
平行纤维与浦肯野细胞之间突触传递的长时程抑制（LTD）是小脑发生的突触可塑性的一个著名例子。一氧化氮（NO）已被认为与其他脑区的突触可塑性有关，但其在小脑LTD中的功能仍存在争议。即使有人提出其参与其中，NO信号转导途径也尚不清楚。一个候选者是环鸟苷酸合成酶，即可溶性鸟苷酸环化酶，其在脑和其他部位的活性受到NO的强烈刺激。通过在小脑切片中对浦肯野细胞进行细胞内记录，我们证明一氧化氮合酶的阻断完全抑制了平行纤维刺激与突触后Ca2+ 峰电位发放配对诱导的LTD。LTD也被细胞内应用1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮所阻断，这是一种最近鉴定出的可溶性鸟苷酸环化酶的强效选择性抑制剂。这些发现表明可溶性鸟苷酸环化酶是小脑LTD所必需的，并表明这种位于浦肯野细胞内的酶在这种形式的突触可塑性中传导NO信号。
