CAMP-DEPENDENT LONG-TERM POTENTIATION OF NITRIC-OXIDE RELEASE FROM CEREBELLAR PARALLEL FIBERS IN RATS

Nitric Oxide (NO) is released from parallel fibers (PFs) after PF stim ulation. NO-cGMP signaling is essential for long-term depression (LTD) in cerebellar PF-Purkinje cell synapses, which also exhibit presynapt ic long-term potentiation (LTP) after tetanic PF stimulation. This LTP is dependent on cAMP but not NO-cGMP signaling. In this study, we ana lyzed long-term changes of NO release from PFs in rat cerebellar slice s 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 pot entiation (LTP,,) by 36 +/- 3% (n = 15) after tetanic PF stimulation. Induction of LTP,, was not affected by Glu receptor antagonists. NO re lease from PFs was also potentiated by L-Arg (ARG) (100 mu M), forskol in (50 mu M), and 8-bromo-cAMP (Br-cAMP) (1 mM) but not by 1,9-dideoxy forskolin (50 mu M), a biologically inactive analog of forskolin. The potentiation induced by forskolin was significantly suppressed by H89 (10 mu M), a blocker of cAMP-dependent protein kinase. The potentiatio n induced by forskolin, but not that induced by Arg, interfered with L TP,,. H89 (10 mu M) and KT5720 (1 mu M), another blocker of cAMP-depen dent protein kinase, but not KT5823 (300 nM), a blocker of cGMP-depend ent protein kinase, significantly suppressed LTP,,. These data indicat e that neural NO release is under activity-dependent control, just as synaptic transmitter release is. LTP,, might play a role in cross talk between presynaptic and postsynaptic plasticity by facilitating NO-cG MP-dependent postsynaptic LTD after induction of cAMP-dependent presyn aptic LTP and LTPNO.