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mGluR7 facilitates extinction of aversive memories and controls amygdala plasticity

Molecular Psychiatry volume 13, pages 970–979 (2008)Cite this article

Abstract

Formation and extinction of aversive memories in the mammalian brain are insufficiently understood at the cellular and molecular levels. Using the novel metabotropic glutamate receptor 7 (mGluR7) agonist AMN082, we demonstrate that mGluR7 activation facilitates the extinction of aversive memories in two different amygdala-dependent tasks. Conversely, mGluR7 knockdown using short interfering RNA attenuated the extinction of learned aversion. mGluR7 activation also blocked the acquisition of Pavlovian fear learning and its electrophysiological correlate long-term potentiation in the amygdala. The finding that mGluR7 critically regulates extinction, in addition to acquisition of aversive memories, demonstrates that this receptor may be relevant for the manifestation and treatment of anxiety disorders.

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Acknowledgements

We acknowledge Professor P Herrling and Dr G Bilbe for giving continuous support and for critical, very helpful discussions. We are deeply grateful to Professor S Nakanishi (Kyoto University, Japan) for providing CHO cell lines stably expressing rat mGluR2 and rat mGluR7a. We thank Drs HR Olpe, CR Pryce and A Lüthi for critically reading the manuscript. Also, we thank H Bürki, S Leonhard, D Fehlmann, E Müller and S Lukic for their expert technical help.

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Author notes

  1. D R Thakker

    Present address: 5Current address: Biosciences R&D, Science & Technology, Medtronic Inc., Minneapolis, MN, USA.,

  2. M Fendt, S Schmid, D R Thakker and L H Jacobson: These authors contributed equally to this work.

Authors and Affiliations

  1. Neuroscience Research, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland

    M Fendt, D R Thakker, L H Jacobson, R Yamamoto, K Mitsukawa, R Maier, P H Kelly, K H McAllister, D Hoyer, H van der Putten, J F Cryan & P J Flor

  2. Tierphysiologie, Zoologisches Institut, Fakultät für Biologie, Universität Tübingen, Tübingen, Germany

    M Fendt & S Schmid

  3. Genome and Proteome Sciences, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Basel, Switzerland

    F Natt & D Hüsken

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  1. M Fendt
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Correspondence to J F Cryan or P J Flor.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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Fendt, M., Schmid, S., Thakker, D. et al. mGluR7 facilitates extinction of aversive memories and controls amygdala plasticity. Mol Psychiatry 13, 970–979 (2008). https://doi.org/10.1038/sj.mp.4002073

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