Modulation of LTP induction by NMDA receptor activation and nitric oxide release

In the CA1 hippocampal region, the induction of long-term potentiation (LTP) requires activation of N-methyl-D-aspartate receptors (NMDARs). However, untimely NMDAR activation either immediately prior to or following tetanic stimulation inhibits LTP generation. This NMDAR-mediated LTP inhibition is overcome by inhibitors of nitric oxide synthase (NOS) and hemoglobin, suggesting the involvement of NO. Additionally, NO inhibitors can promote the ability of weak tetanic stimuli to produce LTP under basal conditions in hippocampal slices. Recent experiments indicate that untimely NMDAR activation contributes to the failure of LTP induction during periods of low glucose exposure and hypoxia. Following hypoxia there is also a delayed form of LTP inhibition that is reversed by NMDAR antagonists and NO inhibitors. These results suggest that there are physiological and pathological conditions during which NMDAR activation and NO release modulate the induction of synaptic plasticity.