Distinct effects of AMPAR subunit depletion on spatial memory

Ahmed Eltokhi; Ilaria Bertocchi; Andrei Rozov; Vidar Jensen; Thilo Borchardt; Amy Taylor; Catia C. Proenca; John Nick P. Rawlins; David M. Bannerman; Rolf Sprengel

iScience (Nov 2023)

Distinct effects of AMPAR subunit depletion on spatial memory

Ahmed Eltokhi,
Ilaria Bertocchi,
Andrei Rozov,
Vidar Jensen,
Thilo Borchardt,
Amy Taylor,
Catia C. Proenca,
John Nick P. Rawlins,
David M. Bannerman,
Rolf Sprengel

Affiliations

Ahmed Eltokhi: Departments of Molecular Neurobiology and Physiology, Max Planck Institute for Medical Research, Heidelberg, Germany; Department of Pharmacolog, University of Washington, Seattle, WA, USA
Ilaria Bertocchi: Departments of Molecular Neurobiology and Physiology, Max Planck Institute for Medical Research, Heidelberg, Germany; Department of Neuroscience Rita Levi Montalcini, University of Turin, 10126 Turin, Italy; Neuroscience Institute - Cavalieri-Ottolenghi Foundation (NICO), Laboratory of Neuropsychopharmacology, Regione Gonzole 10, Orbassano, 10043 Torino, Italy
Andrei Rozov: Departments of Molecular Neurobiology and Physiology, Max Planck Institute for Medical Research, Heidelberg, Germany; Institute of Neuroscience, Lobachevsky State University of Nizhniy, 603022 Novgorod, Russia; Federal Center of Brain Research and Neurotechnology, 117997 Moscow, Russia
Vidar Jensen: Department of Molecular Medicine, Division of Physiology, Institute of Basic Medical Sciences, University of Oslo, 0372 Oslo, Norway
Thilo Borchardt: Departments of Molecular Neurobiology and Physiology, Max Planck Institute for Medical Research, Heidelberg, Germany
Amy Taylor: Department of Experimental Psychology, University of Oxford, Oxford, UK
Catia C. Proenca: Departments of Molecular Neurobiology and Physiology, Max Planck Institute for Medical Research, Heidelberg, Germany
John Nick P. Rawlins: Department of Experimental Psychology, University of Oxford, Oxford, UK
David M. Bannerman: Department of Experimental Psychology, University of Oxford, Oxford, UK; Corresponding author
Rolf Sprengel: Departments of Molecular Neurobiology and Physiology, Max Planck Institute for Medical Research, Heidelberg, Germany; Corresponding author

Journal volume & issue: Vol. 26, no. 11
p. 108116

Abstract

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Summary: Pharmacological studies established a role for AMPARs in the mammalian forebrain in spatial memory performance. Here we generated global GluA1/3 double knockout mice (Gria1/3−/−) and conditional knockouts lacking GluA1 and GluA3 AMPAR subunits specifically from principal cells across the forebrain (Gria1/3ΔFb). In both models, loss of GluA1 and GluA3 resulted in reduced hippocampal GluA2 and increased levels of the NMDAR subunit GluN2A. Electrically-evoked AMPAR-mediated EPSPs were greatly diminished, and there was an absence of tetanus-induced LTP. Gria1/3−/− mice showed premature mortality. Gria1/3ΔFb mice were viable, and their memory performance could be analyzed. In the Morris water maze (MWM), Gria1/3ΔFb mice showed profound long-term memory deficits, in marked contrast to the normal MWM learning previously seen in single Gria1−/− and Gria3−/− knockout mice. Our results suggest a redundancy of function within the pool of available ionotropic glutamate receptors for long-term spatial memory performance.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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