title: AMPA receptor activation causes silencing of AMPA receptor-mediated synaptic transmission in the developing hippocampus.
abstract: Agonist-induced internalization of transmembrane receptors is a widespread biological phenomenon that also may serve as a mechanism for synaptic plasticity. Here we show that the agonist AMPA causes a depression of AMPA receptor (AMPAR) signaling at glutamate synapses in the CA1 region of the hippocampus in slices from developing, but not from mature, rats. This developmentally restricted agonist-induced synaptic depression is expressed as a total loss of AMPAR signaling, without affecting NMDA receptor (NMDAR) signaling, in a large proportion of the developing synapses, thus creating AMPAR silent synapses. The AMPA-induced AMPAR silencing is induced independently of activation of mGluRs and NMDARs, and it mimics and occludes stimulus-induced depression, suggesting that this latter form of synaptic plasticity is expressed as agonist-induced removal of AMPARs. Induction of long-term potentiation (LTP) rendered the developing synapses resistant to the AMPA-induced depression, indicating that LTP contributes to the maturation-related increased stability of these synapses. Our study shows that agonist binding to AMPARs is a sufficient triggering stimulus for the creation of AMPAR silent synapses at developing glutamate synapses.
authors.affiliation: Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. pontus.wasling@physiol.gu.se
authors.forename: Pontus
authors.initials: P
authors.lastname: Wasling
authors.forename: Joakim
authors.initials: J
authors.lastname: Strandberg
authors.forename: Eric
authors.initials: E
authors.lastname: Hanse
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000819:agonists / Q000378:metabolism*; D009435:Synaptic Transmission; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D018091:Receptors, AMPA; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid