title: Amyloid-β effects on synapses and memory require AMPA receptor subunit GluA3.
abstract: Amyloid-β (Aβ) is a prime suspect for causing cognitive deficits during the early phases of Alzheimer's disease (AD). Experiments in AD mouse models have shown that soluble oligomeric clusters of Aβ degrade synapses and impair memory formation. We show that all Aβ-driven effects measured in these mice depend on AMPA receptor (AMPAR) subunit GluA3. Hippocampal neurons that lack GluA3 were resistant against Aβ-mediated synaptic depression and spine loss. In addition, Aβ oligomers blocked long-term synaptic potentiation only in neurons that expressed GluA3. Furthermore, although Aβ-overproducing mice showed significant memory impairment, memories in GluA3-deficient congenics remained unaffected. These experiments indicate that the presence of GluA3-containing AMPARs is critical for Aβ-mediated synaptic and cognitive deficits.
authors.affiliation: Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, 1105BA, The Netherlands.
authors.forename: Niels R
authors.initials: NR
authors.lastname: Reinders
authors.affiliation: Center for Neural Circuits and Behavior, Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093; Section of Neurobiology, Division of Biology, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Pao
authors.affiliation: Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, 1105BA, The Netherlands.
authors.forename: Maria C
authors.initials: MC
authors.lastname: Renner
authors.affiliation: Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, 1105BA, The Netherlands.
authors.forename: Carla M
authors.initials: CM
authors.lastname: da Silva-Matos
authors.affiliation: Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, 1105BA, The Netherlands.
authors.forename: Tessa R
authors.initials: TR
authors.lastname: Lodder
authors.affiliation: Center for Neural Circuits and Behavior, Department of Neuroscience, University of California, San Diego, La Jolla, CA 92093; Section of Neurobiology, Division of Biology, University of California, San Diego, La Jolla, CA 92093 h.kessels@nin.knaw.nl rmalinow@ucsd.edu.
authors.forename: Roberto
authors.initials: R
authors.lastname: Malinow
authors.affiliation: Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, 1105BA, The Netherlands; h.kessels@nin.knaw.nl rmalinow@ucsd.edu.
authors.forename: Helmut W
authors.initials: HW
authors.lastname: Kessels
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D016466:CHO Cells; D003213:Conditioning, Psychological; D003412:Cricetulus; D049229:Dendritic Spines; D005239:Fear / Q000523:psychology; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D017774:Long-Term Potentiation; D008297:Male; D008564:Membrane Potentials; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D018091:Receptors, AMPA; C104723:glutamate receptor ionotropic, AMPA 3
keywords: AMPA; Alzheimer; amyloid; synapse