High-frequency stimulation (HFS) of corticostriatal glutamatergic fibers induces long-term depression (LTD) of excitatory synaptic potentials recorded from striatal spiny neurons. This form of LTD can be mimicked by zaprinast, a selective inhibitor of cGMP phosphodiesterases (PDEs). Biochemical analysis shows that most of the striatal cGMP PDE activity is calmodulin-dependent and inhibited by zaprinast. The zaprinast-induced LTD occludes further depression by tetanic stimulation and vice versa. Both forms of synaptic plasticity are blocked by intracellular 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin- 1-one (ODQ), a selective inhibitor of soluble guanylyl cyclase, indicating that an increased cGMP production in the spiny neuron is a key step. Accordingly, intracellular cGMP, activating protein kinase G (PKG), also induces LTD. Nitric oxide synthase (NOS) inhibitors N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) and 7-nitroindazole monosodium salt (7-NINA) block LTD induced by either HFS or zaprinast, but not that induced by cGMP. LTD is also induced by the NO donors S-nitroso-N-acetylpenicillamine (SNAP) and hydroxylamine. SNAP-induced LTD occludes further depression by HFS or zaprinast, and it is blocked by intracellular ODQ but not by L-NAME. Intracellular application of PKG inhibitors blocks LTD induced by HFS, zaprinast, and SNAP. Electron microscopy immunocytochemistry shows the presence of NOS-positive terminals of striatal interneurons forming synaptic contacts with dendrites of spiny neurons. These findings represent the first demonstration that the NO/cGMP pathway exerts a feedforward

A critical role of the nitric oxide/cGMP pathway in corticostriatal long-term depression / Calabresi, Paolo; Gubellini, Paolo; Centonze, Diego; Sancesario, Giuseppe; Morello, Maria; Giorgi, Mauro; Pisani, Antonio; Bernardi, Giorgio. - In: THE JOURNAL OF NEUROSCIENCE. - ISSN 0270-6474. - STAMPA. - 19:7(1999), pp. 2489-2499.

A critical role of the nitric oxide/cGMP pathway in corticostriatal long-term depression

GIORGI, MAURO;
1999

Abstract

High-frequency stimulation (HFS) of corticostriatal glutamatergic fibers induces long-term depression (LTD) of excitatory synaptic potentials recorded from striatal spiny neurons. This form of LTD can be mimicked by zaprinast, a selective inhibitor of cGMP phosphodiesterases (PDEs). Biochemical analysis shows that most of the striatal cGMP PDE activity is calmodulin-dependent and inhibited by zaprinast. The zaprinast-induced LTD occludes further depression by tetanic stimulation and vice versa. Both forms of synaptic plasticity are blocked by intracellular 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin- 1-one (ODQ), a selective inhibitor of soluble guanylyl cyclase, indicating that an increased cGMP production in the spiny neuron is a key step. Accordingly, intracellular cGMP, activating protein kinase G (PKG), also induces LTD. Nitric oxide synthase (NOS) inhibitors N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) and 7-nitroindazole monosodium salt (7-NINA) block LTD induced by either HFS or zaprinast, but not that induced by cGMP. LTD is also induced by the NO donors S-nitroso-N-acetylpenicillamine (SNAP) and hydroxylamine. SNAP-induced LTD occludes further depression by HFS or zaprinast, and it is blocked by intracellular ODQ but not by L-NAME. Intracellular application of PKG inhibitors blocks LTD induced by HFS, zaprinast, and SNAP. Electron microscopy immunocytochemistry shows the presence of NOS-positive terminals of striatal interneurons forming synaptic contacts with dendrites of spiny neurons. These findings represent the first demonstration that the NO/cGMP pathway exerts a feedforward
Calmodulin-dependent phosphodiesterases; Electron microscopy; Intracellular recordings; Nitric oxide synthase; Striatum; Zaprinast; Neuroscience (all); Medicine (all)
01 Pubblicazione su rivista::01a Articolo in rivista
A critical role of the nitric oxide/cGMP pathway in corticostriatal long-term depression / Calabresi, Paolo; Gubellini, Paolo; Centonze, Diego; Sancesario, Giuseppe; Morello, Maria; Giorgi, Mauro; Pisani, Antonio; Bernardi, Giorgio. - In: THE JOURNAL OF NEUROSCIENCE. - ISSN 0270-6474. - STAMPA. - 19:7(1999), pp. 2489-2499.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/979866
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