Long-term potentiation is a long-lasting, use-dependent increase in the strength of synaptic connections. We investigated the role of nitric oxide (NO) in determining the duration of potentiation induced by high frequency stimulation of afferents in the CAI region of the rat hippocampus. The calcium/calmodulin-dependent production of NO can be initiated by activation of excitatory amino acid receptors and results in increased levels of cGMP in target cells. Here we report that only a relatively short-term potentiation can be induced in the presence of nitr-l-arginine methyl ester (l-NAME), an NO synthase inhibitor. The effects of l-NAME on the duration of potentiation are partially reversed by coadministration of l-arginine, a precursor of neuronal NO, and by dibutyryl cGMP. Hemoglobin, which binds extracellular NO, also shortens the duration of stimulus-induced potentiation. The results suggest a role for NO in the maintenance of activity-dependent synaptic enhancements, possibly via the generation of cGMP.
Bibliographical noteFunding Information:
This work was supported by USPHS grant #ROl-DA-04274 to C. L. W. and by grants from the University of Minnesota Graduate School to P. F. C. We would like to thank Nancy Peterson for technical advice and Michael Mauk, David Wyllie, Steven Traynelis, and Edward Kairiss for critical comments on the manuscript. We aregrateful to Sigma Chemical Company for their gift of DiBcGMP.