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The Journal of Neuroscience, November 1, 1998, 18(21):8551-8558

cAMP-Dependent Long-Term Potentiation of Nitric Oxide Release from Cerebellar Parallel Fibers in Rats

Shinji Kimura1, 2, Seiji Uchiyama2, Hideaki E. Takahashi2, and Katsuei Shibuki1

1 Department of Neurophysiology, Brain Research Institute, and 2 Department of Orthopedic Surgery, School of Medicine, Niigata University, Niigata 951-8585, Japan

Nitric Oxide (NO) is released from parallel fibers (PFs) after PF stimulation. NO-cGMP signaling is essential for long-term depression (LTD) in cerebellar PF-Purkinje cell synapses, which also exhibit presynaptic long-term potentiation (LTP) after tetanic PF stimulation. This LTP is dependent on cAMP but not NO-cGMP signaling. In this study, we analyzed long-term changes of NO release from PFs in rat cerebellar slices using electrochemical NO probes. Repetitive PF stimulation at 10 Hz for 2 sec elicited a transient increase in NO concentration (2.2 ± 0.1 nM; mean ± SEM; n = 116). This NO release exhibited long-term potentiation (LTPNO) by 36 ± 3% (n = 15) after tetanic PF stimulation. Induction of LTPNO was not affected by Glu receptor antagonists. NO release from PFs was also potentiated by L-Arg (ARG) (100 µM), forskolin (50 µM), and 8-bromo-cAMP (Br-cAMP) (1 mM) but not by 1,9-dideoxyforskolin (50 µM), a biologically inactive analog of forskolin. The potentiation induced by forskolin was significantly suppressed by H89 (10 µM), a blocker of cAMP-dependent protein kinase. The potentiation induced by forskolin, but not that induced by Arg, interfered with LTPNO. H89 (10 µM) and KT5720 (1 µM), another blocker of cAMP-dependent protein kinase, but not KT5823 (300 nM), a blocker of cGMP-dependent protein kinase, significantly suppressed LTPNO. These data indicate that neural NO release is under activity-dependent control, just as synaptic transmitter release is. LTPNO might play a role in cross talk between presynaptic and postsynaptic plasticity by facilitating NO-cGMP-dependent postsynaptic LTD after induction of cAMP-dependent presynaptic LTP and LTPNO.

Key words: nitric oxide; cAMP; cGMP; long-term potentiation; cerebellum; parallel fiber


Copyright © 1998 Society for Neuroscience  0270-6474/98/18218551-08$05.00/0


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