Hippocampal mossy fiber long-term depression in Grm2/3 double knockout mice

Authors

  • Louisa Lyon,

    1. Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
    2. University Department of Psychiatry, University of Oxford, Oxford, United Kingdom
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  • Melodie Borel,

    1. Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
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  • Miriam CarriÓn,

    1. Department of Physiology, Anatomy and Cellular Biology, University Pablo de Olavide, Ctra. de Utrera, Km. 1, 41013 Seville, Spain
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  • James N.C. Kew,

    1. Neurosciences CEDD, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex, United Kingdom
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  • Corrado Corti,

    1. Neurosciences CEDD, GlaxoSmithKline, Via Fleming 4, Verona, Italy
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  • Paul J. Harrison,

    1. University Department of Psychiatry, University of Oxford, Oxford, United Kingdom
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  • Philip W.J. Burnet,

    1. University Department of Psychiatry, University of Oxford, Oxford, United Kingdom
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  • Ole Paulsen,

    Corresponding author
    1. Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
    2. Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, United Kingdom
    • Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, United Kingdom
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  • Antonio RodrÍGuez-Moreno

    1. Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
    2. Department of Physiology, Anatomy and Cellular Biology, University Pablo de Olavide, Ctra. de Utrera, Km. 1, 41013 Seville, Spain
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Abstract

Group II metabotropic glutamate receptors (mGluR2, encoded by Grm2, and mGluR3, encoded by Grm3) are inhibitory autoreceptors that negatively modulate the adenylate cyclase signaling cascade. Within the hippocampus, mGluR2 is believed to play a key role in the induction of long-term depression (LTD) at mossy fiber-CA3 synapses. Here, we used Grm2/3 double knockout (dko) mice to investigate to what extent group II mGluRs are necessary for mossy fiber LTD. Surprisingly, we found that these mice displayed prominent mossy fiber LTD. However, the induction of this form of LTD was sensitive to the external Ca2+ concentration. Mossy fiber LTD in Grm2/3 dko mice was indistinguishable from that in wild-type mice at 4 mM Ca2+, but largely absent at 2 mM external Ca2+. Mossy fiber LTD in Grm2/3 dko mice was not blocked by the N-methyl-D-aspartic acid (NMDA) receptor antagonist D-AP5, confirming that the observed response did not reflect NMDA receptor-dependent LTD in contaminating associational-commissural fibers, and enabling us to use the NMDA receptor-mediated EPSC to monitor mossy fiber LTD. Using whole-cell recordings, we demonstrated that LTD of the NMDA receptor-mediated EPSC in Grm2/3 dko mice was not affected by intracellular application of BAPTA and CsF to block postsynaptic Ca2+ and G-protein-mediated effects. This presynaptic LTD was, however, blocked by the AMPA/kainate receptor antagonist, NBQX. Thus, an activity-dependent, external Ca2+ concentration-sensitive form of mossy fiber LTD can be induced in Grm2/3 dko mice. Two mGluR antagonists also failed to block mossy fiber LTD under 4 mM conditions in wild-type mice, strengthening the conclusion that group II mGluRs are not obligatory for mossy fiber LTD. Synapse, 2011. © 2011 Wiley-Liss, Inc.

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