A Role for Endothelial NO Synthase in LTP Revealed by Adenovirus-Mediated Inhibition and Rescue
Pharmacological studies support the idea that nitric oxide (NO) serves as a retrograde messenger during long-term potentiation (LTP) in area CA1 of the hippocampus. Mice with a defective form of the gene for neuronal NO synthase (nNOS), however, exhibit normal LTP. The myristoyl protein endothelial NOS (eNOS) is present in the dendrites of CA1 neurons. Recombinant adenovirus vectors containing either a truncated eNOS (a putative dominant negative) or an eNOS fused to a transmembrane protein were used to demonstrate that membrane-targeted eNOS is required for LTP. The membrane localization of eNOS may optimally position the enzyme both to respond to Ca^(2+) influx and to release NO into the extracellular space during LTP induction.
© 1996 American Association for the Advancement of Science. 27 August 1996; Accepted 23 October 1996. We thank T. Michel for sharing various eNOS cDNAs and unpublished results, B. Seed for CD8 cDNA, A. Berk and L. Wu for Ad-lacZ, and G. Laurent for technical assistance and discussion. Supported by European Molecular Biology Organization grant ALTF 168-1996 (M.L.), National Institute of Mental Health grant 49176 (N.D.), NIH grant NS37292 (E.M.S.), and a Beckman Young Investigator award (E.M.S.)