Transient synaptic activation of NMDA receptors leads to the insertion of native AMPA receptors at hippocampal neuronal plasma membranes

The molecular mechanisms underlying long-term potentiation (LTP) of excitat ory synaptic transmission in the hippocampus are not well understood. Trans ient depolarisation of cultured postnatal hippocampal neurones (3x1 s expos ure to 90 mm K+) induces a form of LTP that is manifest primarily as an inc rease in mEPSC frequency. Site-directed antibodies that recognise an extrac ellular region of all AMPA receptor (AMPAR) subunits (GluR1-4) were used fo r the immunolabelling of living neurones. These antibodies were raised in t wo species to enable sequential immunofluorescent labelling of individual l iving neurones before and after the induction of LTP. High K+ treatment res ulted in the appearance of new AMPAR clusters at sites on the neuronal surf ace that previously lacked detectable AMPARs. The appearance of new AMPAR c lusters was NMDA receptor (NMDAR)-dependent since it was antagonised by the application of NMDAR antagonists. Our data indicate that the transient syn aptic activation of NMDARs can lead to the insertion of native AMPARs at si tes on the neuronal membrane that initially lacks AMPARs. (C) 2001 Publishe d by Elsevier Science Ltd.