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Next Article 
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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