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Forebrain-specific knockout of B-raf kinase leads to deficits in hippocampal long-term potentiation, learning, and memory

Authors

  • Adele P. Chen,

    1. Departments of Neurobiology, Psychiatry and Psychology, Brain Research Institute, University of California, Los Angeles, California
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  • Masuo Ohno,

    1. Departments of Neurobiology, Psychiatry and Psychology, Brain Research Institute, University of California, Los Angeles, California
    Current affiliation:
    1. Department of Physiology, Northwestern University Medical School, Chicago, IL 60611-3008
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  • K. Peter Giese,

    1. Departments of Neurobiology, Psychiatry and Psychology, Brain Research Institute, University of California, Los Angeles, California
    Current affiliation:
    1. Wolfson Institute for Biomedical Research, University College London, London, WC1E 6BT United Kingdom
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  • Ralf Kühn,

    1. Department of Genetics, University of Köln, Köln, Germany
    Current affiliation:
    1. ARTEMIS Pharmaceuticals GmbH, Köln, Germany
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  • Rachel L. Chen,

    1. Departments of Neurobiology, Psychiatry and Psychology, Brain Research Institute, University of California, Los Angeles, California
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  • Alcino J. Silva

    Corresponding author
    1. Departments of Neurobiology, Psychiatry and Psychology, Brain Research Institute, University of California, Los Angeles, California
    • Departments of Neurobiology, Psychiatry and Psychology, Brain Research Institute, University of California, Los Angeles, CA 90095-1761
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Abstract

Raf kinases are downstream effectors of Ras and upstream activators of the MEK-ERK cascade. Ras and MEK-ERK signaling play roles in learning and memory (L&M) and neural plasticity, but the roles of Raf kinases in L&M and plasticity are unclear. Among Raf isoforms, B-raf is preferentially expressed in the brain. To determine whether B-raf has a role in synaptic plasticity and L&M, we used the Cre-LoxP gene targeting system to derive forebrain excitatory neuron B-raf knockout mice. This conditional knockout resulted in deficits in ERK activation and hippocampal long-term potentiation (LTP) and impairments in hippocampus-dependent L&M, including spatial learning and contextual discrimination. Despite the widespread expression of B-raf, this mutation did not disrupt other forms of L&M, such as cued fear conditioning and conditioned taste aversion. Our findings demonstrate that B-raf plays a role in hippocampal ERK activation, synaptic plasticity, and L&M. © 2005 Wiley-Liss, Inc.

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