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Optical activation of endogenous metabotropic glutamate receptor 4 (mGlu4) in the amygdala dynamically regulates symptoms associated with persistent inflammatory pain

Molecular Psychiatry volume 23, page 489 (2018)Cite this article

Using confocal microscopy, intense mGlu4 immunoreactivity was observed in the soma and dendrites of neurons neighboring the intercalated cell clusters in the mouse amygdala, adjacent to mGlu1a-positive GABAergic projection neurons. A moderate staining was also observed within the basolateral complex, and in particular, the lateral amygdala, whereas the central nucleus of the amygdala (CeA) was mostly devoid of specific staining (a, b). Photopharmacology was used to investigate the regulatory role of amygdala mGlu4 receptors on sensory and emotional behaviors associated with persistent inflammatory pain. To this end, we used a small diffusible photoswitchable positive allosteric modulator of mGlu4 named optogluram that allows optical control of endogenous mGlu4 in vivo (c). Ligands and light were directly applied in the amygdala of freely behaving mice through stereotaxically implanted hybrid optic and fluid cannulas (d). Through optical control of mGlu4, sensory and emotional behaviors were rapidly and reversibly inhibited, as exemplified here by allodynia (e). BA, basal amygdale; CeA, central amygdala; LA, lateral amygdala; mITCd, medial dorsal intercalated cell cluster; mITCv, medial ventral ITC. For more information on this topic, please refer to the article by Zussy et al. on pages 509–520.

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Author notes

  1. D De Bundel

    Present address: 10Current address: Department of Pharmaceutical Chemistry and Drug Analysis, Center for Neurosciences, Vrije Universiteit Brussel, Brussels, Belgium.,

Authors and Affiliations

  1. Institut de Génomique Fonctionnelle, CNRS, UMR-5203, Université de Montpellier, Montpellier, France

    C Zussy, X Rovira, D De Bundel, F Malhaire, E Valjent, J-P Pin & C Goudet

  2. INSERM, U1191, Montpellier, France

    C Zussy, X Rovira, D De Bundel, F Malhaire, E Valjent, J-P Pin & C Goudet

  3. MCS, Laboratory of Medicinal Chemistry, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, Spain

    X Gómez-Santacana & A Llebaria

  4. Laboratory of Molecular Neuropharmacology and Bioinformatics, Institut de Neurociències and Unitat de Bioestadística, Universitat Autònoma de Barcelona, Bellaterra, Spain

    X Gómez-Santacana & J Giraldo

  5. Department of Pharmacology, Innsbruck Medical University, Innsbruck, Austria

    S Ferrazzo & F Ferraguti

  6. Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany

    D Bosch, D Asede & I Ehrlich

  7. Werner Reichardt Centre for Integrative Neuroscience, University of Tübingen, Tübingen, Germany

    D Bosch, D Asede & I Ehrlich

  8. Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, CNRS UMR8601, Université Paris Descartes, Sorbonne Paris Cité, Paris, France

    F Acher

  9. Network Biomedical Research Center on Mental Health (CIBERSAM), Madrid, Spain

    J Giraldo

Authors
  1. C Zussy
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  2. X Gómez-Santacana
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  3. X Rovira
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  4. D De Bundel
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  5. S Ferrazzo
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  6. D Bosch
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  7. D Asede
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  8. F Malhaire
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  9. F Acher
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  10. J Giraldo
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  11. E Valjent
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  12. I Ehrlich
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  13. F Ferraguti
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  14. J-P Pin
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  15. A Llebaria
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  16. C Goudet
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Zussy, C., Gómez-Santacana, X., Rovira, X. et al. Optical activation of endogenous metabotropic glutamate receptor 4 (mGlu4) in the amygdala dynamically regulates symptoms associated with persistent inflammatory pain. Mol Psychiatry 23, 489 (2018). https://doi.org/10.1038/mp.2018.4

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