CGG trinucleotide repeat length modulates neural plasticity and spatiotemporal processing in a mouse model of the fragile X premutation

Authors

  • Michael R. Hunsaker,

    Corresponding author
    1. Department of Neurological Surgery, School of Medicine, University of California, Davis; Davis, California
    • Department of Neurological Surgery, 1544 Newton Court, Davis, CA 95616, USA
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  • Kyoungmi Kim,

    1. Division of Biostatistics, Department of Public Health Sciences, School of Medicine, University of California, Davis; Davis, California
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  • Rob Willemsen,

    1. CBG-Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
    2. NeuroTherapeutic Research Institute, University of California, Davis, Davis, California
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  • Robert F. Berman

    1. Department of Neurological Surgery, School of Medicine, University of California, Davis; Davis, California
    2. NeuroTherapeutic Research Institute, University of California, Davis, Davis, California
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Abstract

The fragile X premutation is a CGG repeat expansion on the FMR1 gene between 55 and 200 repeats in length. It has been proposed that impaired spatiotemporal function underlies cognitive deficits in genetic disorders, including the fragile X premutation. This study characterized the role of the premutation for cognitive function by demonstrating CGG KI mice with 70–198 CGG repeats show deficits across tasks requiring spatial and temporal pattern separation. To elucidate mechanisms whereby CGG repeats affect spatiotemporal processing, hippocampal slices were evaluated for LTP, LTD, and mGluR1/5 LTD. Increasing CGG repeat length modulated the induction of LTP, LTD, and mGluR1/5 LTD, as well as behavioral tasks emphasizing spatiotemporal processing. Despite the deficits in the induction of all forms of plasticity, there were no differences in expression of plasticity once evoked. These data provide evidence for a neurocognitive endophenotype in the CGG KI mouse model of the premutation in which CGG repeat length negatively modulates plasticity and spatiotemporal attention. © 2012 Wiley Periodicals, Inc.

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