Impairment of neocortical long-term potentiation in mice deficient of endothelial nitric oxide synthase

The role of the possible retrograde messenger nitric oxide (NO) in the indu ction of long-term potentiation (LTP) was studied in supragranular layers o f somatosensory cortical slices obtained from adult mice. High-frequency st imulation produced a slowly rising, long-lasting (50 min) and significant ( P < 0.001) increase in the extracellular synaptic response by 23%. The indu ction of LTP was independent from activation of N-methyl-D-aspartate (NMDA) receptors, but prevented by bath application of N-G-nitro-L-arginine methy l ester (L-NAME), indicating that one or several of the different NO syntha ses (NOS) produced NO within the postsynaptic neuron. No LTP could be induc ed in knockout mice lacking the endothelial NOS (eNOS) isoform. These data suggest that eNOS is involved in an NMDA receptor-independent form of LTP i n the rodent cerebral cortex.