Dynamic regulation of NMDA receptor transmission

N-methyl-D-aspartate receptors (NMDARs) are critical for establishing, maintaining, and modifying glutamatergic synapses in an activity-dependent manner. The subunit composition, synaptic expression, and some of the properties of NMDARs are regulated by synaptic activity, affecting processes like synaptic plasticity. NMDAR transmission is dynamic, and we were interested in studying the effect of acute low or null synaptic activity on NMDA receptors and its implications for synaptic plasticity. Periods of no stimulation or low-frequency stimulation increased NMDAR transmission. Changes became stable after periods of 20 min of low or no stimulation. These changes in transmission have a postsynaptic origin and are explained by incorporation of GluN2B-containing receptors to synapses. Importantly, periods of low or no stimulation facilitate long-term potentiation induction. Moreover, recovery after a weak preconditioning stimulus that normally blocks subsequent potentiation is facilitated by a nonstimulation period. Thus synaptic activity dynamically regulates the level of NMDAR transmission adapting constantly the threshold for plasticity.