title: Glutamate receptor subunit GluA1 is necessary for long-term potentiation and synapse unsilencing, but not long-term depression in mouse hippocampus.
abstract: Receptor subunit composition is believed to play a major role in the synaptic trafficking of AMPA receptors (AMPARs), and thus in activity-dependent synaptic plasticity. To isolate a physiological role of GluA1-containing AMPARs in area CA3 of the hippocampus, pair recordings were performed in organotypic hippocampal slices taken from genetically modified mice lacking the GluA1 subunit. We report here that long-term potentiation (LTP) is impaired not only at active but also at silent synapses when the GluA1 subunit is absent. The GluA1 knockout mice also exhibited reduced AMPAR-mediated evoked currents between pairs of CA3 pyramidal neurons under baseline conditions suggesting a significant role for GluA1-containing AMPARs in regulating basal synaptic transmission. In two independent measures, however, long-term depression (LTD) was unaffected in tissue from these mice. These data provide a further demonstration of the fundamental role that GluA1-containing AMPARs play in activity-dependent increases in synaptic strength but do not support a GluA1-dependent mechanism for reductions in synaptic strength.
authors.affiliation: Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Joel C
authors.initials: JC
authors.lastname: Selcher
authors.forename: Weifeng
authors.initials: W
authors.lastname: Xu
authors.forename: Jesse E
authors.initials: JE
authors.lastname: Hanson
authors.forename: Robert C
authors.initials: RC
authors.lastname: Malenka
authors.forename: Daniel V
authors.initials: DV
authors.lastname: Madison
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000494:pharmacology; D001703:Biophysics; D056654:CA3 Region, Hippocampal / Q000166:cytology*; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D011810:Quinoxalines / Q000494:pharmacology; D018091:Receptors, AMPA / Q000172:deficiency / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013569:Synapses / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D001640:Bicuculline; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline