AMPA signalling in nascent glutamatergic synapses: there and not there!

Nascent glutamatergic synapses are thought to be equipped with only NMDA receptors and to mature in a stepwise fashion when AMPA receptors are acquired later, through specific patterns of activity. We review recent data suggesting that AMPA receptors are in fact present in the nascent synapse but in a labile state. The nascent synapse can easily switch between AMPA-signalling and AMPA-silent states in a manner not requiring activation of NMDA receptors or metabotropic glutamate receptors. NMDA receptor activation by correlated presynaptic and postsynaptic activity can switch the nascent synapse to a mature, more stable state, in which AMPA receptor signalling is modified only through conventional plasticity processes. Thus, the AMPA receptor silence of nascent glutamatergic synapses depends on the synaptic activation history rather than on the nascent state itself.