title: Importance of AMPA receptors for hippocampal synaptic plasticity but not for spatial learning.
abstract: Gene-targeted mice lacking the L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunit GluR-A exhibited normal development, life expectancy, and fine structure of neuronal dendrites and synapses. In hippocampal CA1 pyramidal neurons, GluR-A-/- mice showed a reduction in functional AMPA receptors, with the remaining receptors preferentially targeted to synapses. Thus, the CA1 soma-patch currents were strongly reduced, but glutamatergic synaptic currents were unaltered; and evoked dendritic and spinous Ca2+ transients, Ca2+-dependent gene activation, and hippocampal field potentials were as in the wild type. In adult GluR-A-/- mice, associative long-term potentiation (LTP) was absent in CA3 to CA1 synapses, but spatial learning in the water maze was not impaired. The results suggest that CA1 hippocampal LTP is controlled by the number or subunit composition of AMPA receptors and show a dichotomy between LTP in CA1 and acquisition of spatial memory.
authors.affiliation: Department of Molecular Neuroscience, Max-Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Zamanillo
authors.forename: R
authors.initials: R
authors.lastname: Sprengel
authors.forename: O
authors.initials: O
authors.lastname: Hvalby
authors.forename: V
authors.initials: V
authors.lastname: Jensen
authors.forename: N
authors.initials: N
authors.lastname: Burnashev
authors.forename: A
authors.initials: A
authors.lastname: Rozov
authors.forename: K M
authors.initials: KM
authors.lastname: Kaiser
authors.forename: H J
authors.initials: HJ
authors.lastname: Köster
authors.forename: T
authors.initials: T
authors.lastname: Borchardt
authors.forename: P
authors.initials: P
authors.lastname: Worley
authors.forename: J
authors.initials: J
authors.lastname: Lübke
authors.forename: M
authors.initials: M
authors.lastname: Frotscher
authors.forename: P H
authors.initials: PH
authors.lastname: Kelly
authors.forename: B
authors.initials: B
authors.lastname: Sommer
authors.forename: P
authors.initials: P
authors.lastname: Andersen
authors.forename: P H
authors.initials: PH
authors.lastname: Seeburg
authors.forename: B
authors.initials: B
authors.lastname: Sakmann
mesh_terms: D000200:Action Potentials; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D018756:GABA Antagonists / Q000494:pharmacology; D015870:Gene Expression; D018390:Gene Targeting; D017781:Genes, Immediate-Early; D018698:Glutamic Acid / Q000494:pharmacology / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology*; D018782:Maze Learning; D051379:Mice; D008810:Mice, Inbred C57BL; D017966:Pyramidal Cells / Q000502:physiology* / Q000648:ultrastructure; D018091:Receptors, AMPA / Q000235:genetics / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission
chemical_list: D001640:Bicuculline; D002118:Calcium; D018756:GABA Antagonists; D018698:Glutamic Acid; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate