Postsynaptic Action Potentials Are Required for Nitric-Oxide-Dependent Long-Term Potentiation in CA1 Neurons of Adult GluR1 Knock-Out and Wild-Type Mice

Neocortical long-term potentiation (LTP) consists of both presynaptic and postsynaptic components that rely on nitric oxide ( NO) and the GluR1 subunit of theAMPAreceptor, respectively. In this study, we found that hippocampal LTP, induced by theta-burst stimulation in mature (> 8-week-old) GluR1 knock-out mice was almost entirely NO dependent and involved both the alpha splice variant of NO synthase-1 and the NO synthase-3 isoforms of NO synthase. Theta-burst induced LTP was also partly NO-dependent in wild-type mice and made up similar to 50% of the potentiation 2 h after tetanus. Theta-burst stimulation reliably produced postsynaptic spikes, including a high probability of complex spikes. Inhibition of postsynaptic somatic spikes with intracellular QX314 or local TTX application prevented LTP in the GluR1 knock-out mice and also blocked the NO component of LTP in wild types. We conclude that theta-burst stimulation is particularly well suited to producing the postsynaptic somatic spikes required for NO-dependent LTP.