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 feed-forward control on the corticostriatal synaptic plasticity.
Calabresi, P., Gubellini, P., Centonze, D., Sancesario, G., Morello, M., Giorgi, M., et al. (1999). A critical role of the nitric oxide/cGMP pathway in corticostriatal long-term depression. THE JOURNAL OF NEUROSCIENCE, 19(7), 2489-2499.
|Tipologia:||Articolo su rivista|
|Citazione:||Calabresi, P., Gubellini, P., Centonze, D., Sancesario, G., Morello, M., Giorgi, M., et al. (1999). A critical role of the nitric oxide/cGMP pathway in corticostriatal long-term depression. THE JOURNAL OF NEUROSCIENCE, 19(7), 2489-2499.|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore MED/26 - Neurologia|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||1-apr-1999|
|Titolo:||A critical role of the nitric oxide/cGMP pathway in corticostriatal long-term depression|
|Autori:||Calabresi, P; Gubellini, P; Centonze, D; Sancesario, G; Morello, M; Giorgi, M; Pisani, A; Bernardi, G|
|Appare nelle tipologie:||01 - Articolo su rivista|