ENDOTHELIAL NOS AND THE BLOCKADE OF LTP BY NOS INHIBITORS IN MICE LACKING NEURONAL NOS

Long-term potentiation (LTP) is a persistent increase in synaptic stre ngth implicated in certain forms of learning and memory. In the CA1 re gion of the hippocampus, LTP is thought to involve the release of one or more retrograde messengers from the postsynaptic cell that act on t he presynaptic terminal to enhance transmitter release. One candidate retrograde messenger is the membrane-permeant gas nitric oxide (NO), w hich in the brain is released after activation of the neuronal-specifi c NO synthase isoform (nNOS). To assess the importance of NO in hippoc ampal synaptic plasticity, LTP was examined in mice where the gene enc oding nNOS was disrupted by gene targeting. In nNOS(-) mice, LTP induc ed by weak intensity tetanic stimulation was normal except for a sligh t reduction in comparison to that in wild-type mice and was blocked by NOS inhibitors, just as it was in wild-type mice. Immunocytochemical studies indicate that in the nNOS(-) mice as in wild-type mice, the en dothelial form of NOS (eNOS) is expressed in CA1 neurons. These findin gs suggest that eNOS, rather than nNOS, generates NO within the postsy naptic cell during LTP.