Activation of extrasynaptic NMDA receptors induces a PKC‐dependent switch in AMPA receptor subtypes in mouse cerebellar stellate cells

The repetitive activation of synaptic glutamate receptors can induce a lasting change in the number or subunit composition of synaptic AMPA receptors (AMPARs). However, NMDA receptors that are present extrasynaptically can also be activated by a burst of presynaptic activity, and thus may be involved in the induction of synaptic plasticity. Here we show that the physiological‐like activation of extrasynaptic NMDARs induces a lasting change in the synaptic current, by changing the subunit composition of AMPARs at the parallel fibre‐to‐cerebellar stellate cell synapse. This extrasynaptic NMDAR‐induced switch in synaptic AMPARs from GluR2‐lacking (Ca 2+ ‐permeable) to GluR2‐containing (Ca 2+ ‐impermeable) receptors requires the activation of protein kinase C (PKC). These results indicate that the activation of extrasynaptic NMDARs by glutamate spillover is an important mechanism that detects the pattern of afferent activity and subsequently exerts a remote regulation of AMPAR subtypes at the synapse via a PKC‐dependent pathway.