Zhuo_1994_Neuroreport_5_1033

Nitric oxide (NO) has been suggested to play the role of retrograde messenger 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 retrograde messenger is that it should also elicit long-lasting enhancement when paired with low-frequency stimulation of the presynaptic fibers. In the present study, we have tested this prediction. We find that NO produces long-lasting depression rather than potentiation when paired with low-frequency stimulation (0.25 Hz). A similar long-lasting depression is produced by 8-Br-cGMP, a cGMP analog, suggesting that NO may produce its effect by activating soluble guanylyl cyclase. These results demonstrate that NO and cGMP modulate synaptic transmission in the hippocampus by frequency-dependent mechanisms, and suggest that NO is most suitable as a retrograde messenger for LTP when the presynaptic neuron fires at high frequencies. By contrast, carbon monoxide (CO) elicits long lasting enhancement at both low and high frequencies.