LONG-TERM POTENTIATION IS REDUCED IN MICE THAT ARE DOUBLY MUTANT IN ENDOTHELIAL AND NEURONAL NITRIC-OXIDE SYNTHASE

Nitric oxide (NO) has been implicated in hippocampal long-term potenti ation (LTP), but LTP is normal in mice with a targeted mutation in the neuronal form of NO synthase (nNOS(-)). LTP was also normal in mice w ith a targeted mutation in endothelial NOS (eNOS(-)), but LTP in strat um radiatum of CA1 was significantly reduced in doubly mutant mice (nN OS(-)/eNOS(-)). By contrast, LTP in stratum oriens was normal in the d oubly mutant mice. These results provide the first genetic evidence th at NOS is involved in LTP in stratum radiatum and suggest that the neu ronal and endothelial forms can compensate for each other in mice with a single mutation. They further suggest that there is also a NOS-inde pendent component of LTP in stratum radiatum and that LTP in stratum o riens is largely NOS independent.