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Circuit mechanisms of GluA1-dependent spatial working memory

Authors

  • Florian Freudenberg,

    Corresponding author
    1. Laboratory of Neural Circuits and Plasticity, University of Southern California, 3641 Watt Way, Los Angeles, California
    2. Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, Heidelberg, Germany
    Current affiliation:
    1. Psychiatric Neurobiology, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany
    • Correspondence to: Florian Freudenberg, Psychiatric Neurobiology, Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Füchsleinstr. 15, 97080 Würzburg, Germany. E-mail: ffreuden@gmail.com

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    • F.F. and V.M. contributed equally to this work.

  • Verena Marx,

    1. Laboratory of Neural Circuits and Plasticity, University of Southern California, 3641 Watt Way, Los Angeles, California
    2. Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, Heidelberg, Germany
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    • F.F. and V.M. contributed equally to this work.

  • Peter H. Seeburg,

    1. Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, Heidelberg, Germany
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  • Rolf Sprengel,

    1. Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, Heidelberg, Germany
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  • Tansu Celikel

    1. Laboratory of Neural Circuits and Plasticity, University of Southern California, 3641 Watt Way, Los Angeles, California
    2. Department of Neurophysiology, Donders Center for Neuroscience, Radboud University Nijmegen, AA Nijmegen, The Netherlands
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ABSTRACT

Spatial working memory (SWM), the ability to process and manipulate spatial information over a relatively short period of time, requires an intact hippocampus, but also involves other forebrain nuclei in both in rodents and humans. Previous studies in mice showed that the molecular mechanism of SWM includes activation of AMPA receptors containing the GluA1 subunit (encoded by gria1) as GluA1 deletion in the whole brain (gria1–/–) results in strong SWM deficit. However, since these mice globally lack GluA1, the circuit mechanisms of GluA1 contribution to SWM remain unknown. In this study, by targeted expression of GluA1 containing AMPA receptors in the forebrain of gria1–/– mice or by removing GluA1 selectively from hippocampus of mice with “floxed” GluA1 alleles (gria1fl/fl), we show that SWM requires GluA1 action in cortical circuits but is only partially dependent on GluA1-containing AMPA receptors in hippocampus. We further show that hippocampal GluA1 contribution to SWM is temporally restricted and becomes prominent at longer retention intervals (≥30 s). These findings provide a novel insight into the neural circuits required for SWM processing and argue that AMPA mediated signaling across forebrain and hippocampus differentially contribute to encoding of SWM. © 2013 Wiley Periodicals, Inc.

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