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Somatic Accumulation of GluA1-AMPA Receptors Leads to Selective Cognitive Impairments in Mice.
Bannerman, David M; Borchardt, Thilo; Jensen, Vidar; Rozov, Andrey; Haj-Yasein, Nadia N; Burnashev, Nail; Zamanillo, Daniel; Bus, Thorsten; Grube, Isabel; Adelmann, Giselind; Rawlins, J Nicholas P; Sprengel, Rolf.
Afiliación
  • Bannerman DM; Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom.
  • Borchardt T; Departments of Molecular Neurobiology and Cell Physiology, Max Planck Institute for Medical Research, Heidelberg, Germany.
  • Jensen V; EW-Nutrition GmbH, Visbek, Germany.
  • Rozov A; Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
  • Haj-Yasein NN; Departments of Molecular Neurobiology and Cell Physiology, Max Planck Institute for Medical Research, Heidelberg, Germany.
  • Burnashev N; Department of Physiology and Pathophysiology, Heidelberg University, Heidelberg, Germany.
  • Zamanillo D; OpenLab of Neurobiology, Kazan Federal University, Kazan, Russia.
  • Bus T; Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
  • Grube I; Departments of Molecular Neurobiology and Cell Physiology, Max Planck Institute for Medical Research, Heidelberg, Germany.
  • Adelmann G; INSERM UMR 1249 Mediterranean Institute of Neurobiology (INMED), Aix-Marseille University Parc Scientifique de Luminy, Marseille, France.
  • Rawlins JNP; Departments of Molecular Neurobiology and Cell Physiology, Max Planck Institute for Medical Research, Heidelberg, Germany.
  • Sprengel R; Esteve Pharmaceuticals, S.A., Barcelona, Spain.
Front Mol Neurosci ; 11: 199, 2018.
Article en En | MEDLINE | ID: mdl-29988555
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Front Mol Neurosci Año: 2018 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: Front Mol Neurosci Año: 2018 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Suiza