NITRIC-OXIDE ACTS DIRECTLY IN THE PRESYNAPTIC NEURON TO PRODUCE LONG-TERM POTENTIATION IN CULTURED HIPPOCAMPAL-NEURONS

Nitric oxide (NO) has been proposed to act as a retrograde messenger d uring long-term potentiation (LTP) in the CA1 region of hippocampus, b ut the inaccessibility of the presynaptic terminal has prevented a def initive test of this hypothesis. Because both sides of the synapse are accessible in cultured hippocampal neurons, we have used this prepara tion to investigate the role of NO. We examined LTP following intra- o r extracellular application of an NO scavanger, an inhibitor of NO syn thase, and a membrane-impermeant NO donor that releases NO only upon p hotolysis with UV light. Our results indicate that NO is produced in t he postsynaptic neuron, travels through the extracellular space, and a cts directly in the presynaptic neuron to produce long-term potentiati on, supporting the hypothesis that NO acts as a retrograde messenger d uring LTP.