Distinct effects of AMPAR subunit depletion on spatial memory
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 fo...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223021934 |
| _version_ | 1797657869154254848 |
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| author | Ahmed Eltokhi Ilaria Bertocchi Andrei Rozov Vidar Jensen Thilo Borchardt Amy Taylor Catia C. Proenca John Nick P. Rawlins David M. Bannerman Rolf Sprengel |
| author_facet | Ahmed Eltokhi Ilaria Bertocchi Andrei Rozov Vidar Jensen Thilo Borchardt Amy Taylor Catia C. Proenca John Nick P. Rawlins David M. Bannerman Rolf Sprengel |
| author_sort | Ahmed Eltokhi |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T17:50:48Z |
| format | Article |
| id | doaj.art-3d19046a94f54e098f4d4195cc9ae8b8 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-11T17:50:48Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-3d19046a94f54e098f4d4195cc9ae8b82023-10-18T04:31:26ZengElsevieriScience2589-00422023-11-012611108116Distinct effects of AMPAR subunit depletion on spatial memoryAhmed Eltokhi0Ilaria Bertocchi1Andrei Rozov2Vidar Jensen3Thilo Borchardt4Amy Taylor5Catia C. Proenca6John Nick P. Rawlins7David M. Bannerman8Rolf Sprengel9Departments of Molecular Neurobiology and Physiology, Max Planck Institute for Medical Research, Heidelberg, Germany; Department of Pharmacolog, University of Washington, Seattle, WA, USADepartments 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, ItalyDepartments 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, RussiaDepartment of Molecular Medicine, Division of Physiology, Institute of Basic Medical Sciences, University of Oslo, 0372 Oslo, NorwayDepartments of Molecular Neurobiology and Physiology, Max Planck Institute for Medical Research, Heidelberg, GermanyDepartment of Experimental Psychology, University of Oxford, Oxford, UKDepartments of Molecular Neurobiology and Physiology, Max Planck Institute for Medical Research, Heidelberg, GermanyDepartment of Experimental Psychology, University of Oxford, Oxford, UKDepartment of Experimental Psychology, University of Oxford, Oxford, UK; Corresponding authorDepartments of Molecular Neurobiology and Physiology, Max Planck Institute for Medical Research, Heidelberg, Germany; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004223021934Molecular neuroscienceCellular neuroscience |
| spellingShingle | Ahmed Eltokhi Ilaria Bertocchi Andrei Rozov Vidar Jensen Thilo Borchardt Amy Taylor Catia C. Proenca John Nick P. Rawlins David M. Bannerman Rolf Sprengel Distinct effects of AMPAR subunit depletion on spatial memory iScience Molecular neuroscience Cellular neuroscience |
| title | Distinct effects of AMPAR subunit depletion on spatial memory |
| title_full | Distinct effects of AMPAR subunit depletion on spatial memory |
| title_fullStr | Distinct effects of AMPAR subunit depletion on spatial memory |
| title_full_unstemmed | Distinct effects of AMPAR subunit depletion on spatial memory |
| title_short | Distinct effects of AMPAR subunit depletion on spatial memory |
| title_sort | distinct effects of ampar subunit depletion on spatial memory |
| topic | Molecular neuroscience Cellular neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223021934 |
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