Activation of silent synapses by rapid activity-dependent synaptic recruitment of AMPA receptors

Many recent studies have shown that excitatory synapses can contain NMDA re ceptor responses in the absence of functional AMPA receptors and are theref ore postsynaptically silent at resting membrane potentials. The activation of silent synapses via the rapid acquisition of AMPA receptor responses may be important in synaptic plasticity and neuronal development. Our recent i mmunocytochemical studies that used cultured hippocampal neurons have provi ded evidence for "morphological silent synapses" that physically contain NM DA receptors but no AMPA receptors. Here we show that the activation of NMD A receptors by spontaneous synaptic activity results in the rapid recruitme nt of AMPA receptors into these morphological silent synapses within minute s. In parallel, we find a significant increase in the frequency of AMPA rec eptor-mediated miniature EPSCs (mEPSCs). NMDA receptor activation also resu lts in a mobilization of calcium/calmodulin (CaM) kinase II to synapses and an increase in the phosphorylation of surface AMPA receptors on the major CaM kinase II phosphorylation site. These results demonstrate that AMPA rec eptors can be modified and recruited rapidly to silent synapses via the act ivation of NMDA receptors by spontaneous synaptic activity.