NITRIC-OXIDE AND CGMP CAN PRODUCE EITHER SYNAPTIC DEPRESSION OR POTENTIATION DEPENDING ON THE FREQUENCY OF PRESYNAPTIC STIMULATION IN THE HIPPOCAMPUS

NITRIC OXIDE (NO) has been suggested to play the role of retrograde me ssenger during long-term potentiation (LTP) in hippocampus. In support of this idea, NO induces LTP when paired with a weak tetanus (50 Hz). An additional criterion that has been proposed for NO being a retrogr ade messenger is that it should also elicit long-lasting enhancement w hen paired with low-frequency stimulation of the presynaptic fibers. I n the present study, we have tested this prediction. We find that NO p roduces long-lasting depression rather than potentiation when paired w ith low-frequency stimulation (0.25 Hz). A similar long-lasting depres sion is produced by 8-Br-cGMP, a cGMP analog, suggesting that NO may p roduce its effect by activating soluble guanyly cyclase. These results demonstrate that NO and cGMP modulate synaptic transmission in the hi ppocampus by frequency-dependent mechanisms, and suggest that NO is mo st suitable as a retrograde messenger for LTP when the presynaptic neu ron fires at high frequencies. By contrast, carbon monoxide (CO) elici ts long lasting enhancement at both low and high frequencies.