Somatic Accumulation of GluA1-AMPA Receptors Leads to Selective Cognitive Impairments in Mice
The GluA1 subunit of the L-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) plays a crucial, but highly selective, role in cognitive function. Here we analyzed AMPAR expression, AMPAR distribution and spatial learning in mice (Gria1R/R), expressing the “trafficking compromised”...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-06-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2018.00199/full |
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| author | David M. Bannerman Thilo Borchardt Thilo Borchardt Vidar Jensen Andrey Rozov Andrey Rozov Andrey Rozov Nadia N. Haj-Yasein Nail Burnashev Nail Burnashev Daniel Zamanillo Daniel Zamanillo Thorsten Bus Isabel Grube Isabel Grube Giselind Adelmann J. Nicholas P. Rawlins Rolf Sprengel Rolf Sprengel |
| author_facet | David M. Bannerman Thilo Borchardt Thilo Borchardt Vidar Jensen Andrey Rozov Andrey Rozov Andrey Rozov Nadia N. Haj-Yasein Nail Burnashev Nail Burnashev Daniel Zamanillo Daniel Zamanillo Thorsten Bus Isabel Grube Isabel Grube Giselind Adelmann J. Nicholas P. Rawlins Rolf Sprengel Rolf Sprengel |
| author_sort | David M. Bannerman |
| collection | DOAJ |
| description | The GluA1 subunit of the L-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) plays a crucial, but highly selective, role in cognitive function. Here we analyzed AMPAR expression, AMPAR distribution and spatial learning in mice (Gria1R/R), expressing the “trafficking compromised” GluA1(Q600R) point mutation. Our analysis revealed somatic accumulation and reduction of GluA1(Q600R) and GluA2, but only slightly reduced CA1 synaptic localization in hippocampi of adult Gria1R/R mice. These immunohistological changes were accompanied by a strong reduction of somatic AMPAR currents in CA1, and a reduction of plasticity (short-term and long-term potentiation, STP and LTP, respectively) in the CA1 subfield following tetanic and theta-burst stimulation. Nevertheless, spatial reference memory acquisition in the Morris water-maze and on an appetitive Y-maze task was unaffected in Gria1R/R mice. In contrast, spatial working/short-term memory during both spontaneous and rewarded alternation tasks was dramatically impaired. These findings identify the GluA1(Q600R) mutation as a loss of function mutation that provides independent evidence for the selective role of GluA1 in the expression of short-term memory. |
| first_indexed | 2024-12-22T08:56:26Z |
| format | Article |
| id | doaj.art-b1bc7d8f548849c9b8a8170e463b858f |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-22T08:56:26Z |
| publishDate | 2018-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-b1bc7d8f548849c9b8a8170e463b858f2022-12-21T18:31:49ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-06-011110.3389/fnmol.2018.00199296113Somatic Accumulation of GluA1-AMPA Receptors Leads to Selective Cognitive Impairments in MiceDavid M. Bannerman0Thilo Borchardt1Thilo Borchardt2Vidar Jensen3Andrey Rozov4Andrey Rozov5Andrey Rozov6Nadia N. Haj-Yasein7Nail Burnashev8Nail Burnashev9Daniel Zamanillo10Daniel Zamanillo11Thorsten Bus12Isabel Grube13Isabel Grube14Giselind Adelmann15J. Nicholas P. Rawlins16Rolf Sprengel17Rolf Sprengel18Department of Experimental Psychology, University of Oxford, Oxford, United KingdomDepartments of Molecular Neurobiology and Cell Physiology, Max Planck Institute for Medical Research, Heidelberg, GermanyEW-Nutrition GmbH, Visbek, GermanyDepartment of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, NorwayDepartments of Molecular Neurobiology and Cell Physiology, Max Planck Institute for Medical Research, Heidelberg, GermanyDepartment of Physiology and Pathophysiology, Heidelberg University, Heidelberg, GermanyOpenLab of Neurobiology, Kazan Federal University, Kazan, RussiaDepartment of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, NorwayDepartments of Molecular Neurobiology and Cell Physiology, Max Planck Institute for Medical Research, Heidelberg, GermanyINSERM UMR 1249 Mediterranean Institute of Neurobiology (INMED), Aix-Marseille University Parc Scientifique de Luminy, Marseille, FranceDepartments of Molecular Neurobiology and Cell Physiology, Max Planck Institute for Medical Research, Heidelberg, GermanyEsteve Pharmaceuticals, S.A., Barcelona, SpainDepartments of Molecular Neurobiology and Cell Physiology, Max Planck Institute for Medical Research, Heidelberg, GermanyInstitute of Anatomy and Cell Biology, University of Freiburg, Freiburg, Germany0Department for Internal Medicine, Klinikum Landkreis Tuttlingen, Tuttlingen, GermanyInstitute of Anatomy and Cell Biology, University of Freiburg, Freiburg, GermanyDepartment of Experimental Psychology, University of Oxford, Oxford, United KingdomDepartments of Molecular Neurobiology and Cell Physiology, Max Planck Institute for Medical Research, Heidelberg, Germany1Institute for Anatomy and Cell Biology, Heidelberg University, Heidelberg, GermanyThe GluA1 subunit of the L-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) plays a crucial, but highly selective, role in cognitive function. Here we analyzed AMPAR expression, AMPAR distribution and spatial learning in mice (Gria1R/R), expressing the “trafficking compromised” GluA1(Q600R) point mutation. Our analysis revealed somatic accumulation and reduction of GluA1(Q600R) and GluA2, but only slightly reduced CA1 synaptic localization in hippocampi of adult Gria1R/R mice. These immunohistological changes were accompanied by a strong reduction of somatic AMPAR currents in CA1, and a reduction of plasticity (short-term and long-term potentiation, STP and LTP, respectively) in the CA1 subfield following tetanic and theta-burst stimulation. Nevertheless, spatial reference memory acquisition in the Morris water-maze and on an appetitive Y-maze task was unaffected in Gria1R/R mice. In contrast, spatial working/short-term memory during both spontaneous and rewarded alternation tasks was dramatically impaired. These findings identify the GluA1(Q600R) mutation as a loss of function mutation that provides independent evidence for the selective role of GluA1 in the expression of short-term memory.https://www.frontiersin.org/article/10.3389/fnmol.2018.00199/fullAMPA receptorsGluA1long-term potentiationMorris water-mazeRNA-editingspatial memory |
| spellingShingle | David M. Bannerman Thilo Borchardt Thilo Borchardt Vidar Jensen Andrey Rozov Andrey Rozov Andrey Rozov Nadia N. Haj-Yasein Nail Burnashev Nail Burnashev Daniel Zamanillo Daniel Zamanillo Thorsten Bus Isabel Grube Isabel Grube Giselind Adelmann J. Nicholas P. Rawlins Rolf Sprengel Rolf Sprengel Somatic Accumulation of GluA1-AMPA Receptors Leads to Selective Cognitive Impairments in Mice Frontiers in Molecular Neuroscience AMPA receptors GluA1 long-term potentiation Morris water-maze RNA-editing spatial memory |
| title | Somatic Accumulation of GluA1-AMPA Receptors Leads to Selective Cognitive Impairments in Mice |
| title_full | Somatic Accumulation of GluA1-AMPA Receptors Leads to Selective Cognitive Impairments in Mice |
| title_fullStr | Somatic Accumulation of GluA1-AMPA Receptors Leads to Selective Cognitive Impairments in Mice |
| title_full_unstemmed | Somatic Accumulation of GluA1-AMPA Receptors Leads to Selective Cognitive Impairments in Mice |
| title_short | Somatic Accumulation of GluA1-AMPA Receptors Leads to Selective Cognitive Impairments in Mice |
| title_sort | somatic accumulation of glua1 ampa receptors leads to selective cognitive impairments in mice |
| topic | AMPA receptors GluA1 long-term potentiation Morris water-maze RNA-editing spatial memory |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2018.00199/full |
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