Synaptic AMPA receptor exchange maintains bidirectional plasticity.
Activity-dependent synaptic delivery of GluR1-, GluR2L-, and GluR4-containing AMPA receptors (-Rs) and removal of GluR2-containing AMPA-Rs mediate synaptic potentiation and depression, respectively. The obvious puzzle is how synapses maintain the capacity for bidirectional plasticity if different AMPA-Rs are utilized for potentiation and depression. Here, we show that synaptic AMPA-R exchange is essential for maintaining the capacity for bidirectional plasticity. The exchange process consists of activity-independent synaptic removal of GluR1-, GluR2L-, or GluR4-containing AMPA-Rs and refilling with GluR2-containing AMPA-Rs at hippocampal and cortical synapses in vitro and in intact brains. In GluR1 and GluR2 knockout mice, initiation or completion of synaptic AMPA-R exchange is compromised, respectively. The complementary AMPA-R removal and refilling events in the exchange process ultimately maintain synaptic strength unchanged, but their long rate time constants ( approximately 15-18 hr) render transmission temporarily depressed in the middle of the exchange. These results suggest that the previously hypothesized "slot" proteins, rather than AMPA-Rs, code and maintain transmission efficacy at central synapses.
McCormack
Stefanie G
SG
Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA.
Stornetta
Ruth L
RL
Zhu
J Julius
JJ
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology*; D004558:Electric Stimulation / Q000379:methods; D049452:Green Fluorescent Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008274:Magnesium / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects / Q000821:virology; D018408:Patch-Clamp Techniques / Q000379:methods; D051381:Rats; D018091:Receptors, AMPA / Q000145:classification / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014738:Vibrissae / Q000294:innervation / Q000502:physiology
D000779:Anesthetics, Local; D049452:Green Fluorescent Proteins; D008274:Magnesium; D018091:Receptors, AMPA; D013779:Tetrodotoxin; C104722:glutamate receptor ionotropic, AMPA 2