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Enhanced odor discrimination and impaired olfactory memory by spatially controlled switch of AMPA Receptors

MPG-Autoren
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Shimshek,  Derya R.
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;

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Bus,  Thorsten
Max Planck Research Group Behavioural Neurophysiology (Andreas T. Schaefer), Max Planck Institute for Medical Research, Max Planck Society;

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Mihaljevic,  André
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;

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Mack,  Volker
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;

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Seeburg,  Peter H.
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;

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Sprengel,  Rolf
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;

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Schaefer,  Andreas T.
Max Planck Research Group Behavioural Neurophysiology (Andreas T. Schaefer), Max Planck Institute for Medical Research, Max Planck Society;
Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society;

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Zitation

Shimshek, D. R., Bus, T., Kim, J.-H., Mihaljevic, A., Mack, V., Seeburg, P. H., et al. (2005). Enhanced odor discrimination and impaired olfactory memory by spatially controlled switch of AMPA Receptors. PLoS Biology, 3(11): 354, pp. 2017-2030. doi:10.1371/journal.pbio.0030354.


Zitierlink: http://hdl.handle.net/11858/00-001M-0000-002A-CAD3-D
Zusammenfassung
Genetic perturbations of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) are widely used to dissect molecular mechanisms of sensory coding, learning, and memory. In this study, we investigated the role of Ca2+-permeable AMPARs in olfactory behavior. AMPAR modification was obtained by depletion of the GluR-B subunit or expression of unedited GluR-B(Q), both leading to increased Ca2+ permeability of AMPARs. Mice with this functional AMPAR switch, specifically in forebrain, showed enhanced olfactory discrimination and more rapid learning in a go/no-go operant conditioning task. Olfactory memory, however, was dramatically impaired. GluR-B depletion in forebrain was ectopically variable ("mosaic") among individuals and strongly correlated with decreased olfactory memory in hippocampus and cortex. Accordingly, memory was rescued by transgenic GluR-B expression restricted to piriform cortex and hippocampus, while enhanced odor discrimination was independent of both GluR-B variability and transgenic GluR-B expression. Thus, correlated differences in behavior and levels of GluR-B expression allowed a mechanistic and spatial dissection of olfactory learning, discrimination, and memory capabilities.