NITRIC-OXIDE SYNTHASE-INDEPENDENT LONG-TERM POTENTIATION IN AREA CA1 OF HIPPOCAMPUS

IN ORDER to elucidate the role of NO in LTP, we have investigated a bi ochemical effector of NO action at hippocampal synapses, guanylyl cycl ase. We have observed that LTP-inducing stimuli elicit an increase in the activity of guanylyl cyclase, an effect blocked by inhibitors of N O synthase. Extracellular application of hemoglobin, which binds NO an d thereby blocks its actions, also attenuated the increase in guanylyl cyclase activity. Taken together, the results provide direct biochemi cal evidence for an elevation of NO levels with LTP-inducing stimulati on, and support the hypothesis that NO can function as a transcellular messenger in the hippocampus. These findings also implicate guanylyl cyclase as a target of NO and demonstrate that while NO is elevated wi th LTP-inducing stimuli, the activity of NO synthase is not necessary for induction of LTP by all stimulus paradigms.