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 CAI of the hippocampus. Mice with a defective form of the gene for ne uronal NO synthase (nNOS), however, exhibit normal LTP. The myristoyl protein endothelial NOS (eNOS) is present in the dendrites of CA1 neur ons. Recombinant adenovirus vectors containing either a truncated eNOS (a putative dominant negative) or an eNOS fused to a transmembrane pr otein 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 Ca2+ influx and to release NO into the extr acellular space during LTP induction.