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Long‐Term Depression in Rat Cerebellum Requires both NO Synthase and NO‐sensitive Guanylyl Cyclase
Author(s) -
Boxall Andrew R.,
Garthwaite John
Publication year - 1996
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1996.tb00743.x
Subject(s) - soluble guanylyl cyclase , cerebellum , synaptic plasticity , long term depression , neuroscience , postsynaptic potential , neurotransmission , nitric oxide , microbiology and biotechnology , chemistry , nitric oxide synthase , purkinje cell , stimulation , cerebellar cortex , intracellular , signal transduction , biology , guanylate cyclase , glutamate receptor , biochemistry , receptor , endocrinology , ampa receptor
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 Ca 2+ 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.