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4-Hz oscillations synchronize prefrontal–amygdala circuits during fear behavior

Nature Neuroscience volume 19, pages 605612 (2016) | Download Citation

Abstract

Fear expression relies on the coordinated activity of prefrontal and amygdala circuits, yet the mechanisms allowing long-range network synchronization during fear remain unknown. Using a combination of extracellular recordings, pharmacological and optogenetic manipulations, we found that freezing, a behavioral expression of fear, temporally coincided with the development of sustained, internally generated 4-Hz oscillations in prefrontal–amygdala circuits. 4-Hz oscillations predict freezing onset and offset and synchronize prefrontal–amygdala circuits. Optogenetic induction of prefrontal 4-Hz oscillations coordinates prefrontal–amygdala activity and elicits fear behavior. These results unravel a sustained oscillatory mechanism mediating prefrontal–amygdala coupling during fear behavior.

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Acknowledgements

We thank the members of the Herry laboratory for discussions and comments on the manuscript and K. Deisseroth (Stanford University) and E. Boyden (Massachusetts Institute of Technology) for generously sharing material. This work was supported by grants from the French National Research Agency (ANR-2010-BLAN-1442-01; ANR-10-EQPX-08 OPTOPATH; LABEX BRAIN ANR 10-LABX-43, LABEX TRAIL ANR 10-LABX-57), the European Research Council (ERC) under the European Union's Seventh Framework Program (FP7/2007-2013)/ERC grant agreement no. 281168, the Conseil Regional d'Aquitaine (C.H.), the Fondation pour la Recherche Médicale (FRM) (F.C.), the CNRS ATIP program (2014) and the city of Paris (Grant Emergence 2014), the French National Research Agency (ANR-10-LABX-54 MEMO LIFE; ANR-11-IDEX-0001-02 PSL) (K.B.), Munich Cluster for Systems Neurology (SyNergy, EXC 1010), Deutsche Forschungsgemeinschaft Priority Program 1665 and 1392 and Bundesministerium für Bildung und Forschung via grant no. 01GQ0440 (Bernstein Centre for Computational Neuroscience Munich) (A.S.) and a scholarship from the Erasmus Mundus program Neurasmus (N.K.).

Author information

Author notes

    • Nikolaos Karalis
    • , Cyril Dejean
    •  & Fabrice Chaudun

    These authors contributed equally to this work.

    • Julien Courtin
    •  & Cyril Herry

    These authors jointly directed this work.

Affiliations

  1. INSERM, Neurocentre Magendie, U862, Bordeaux, France.

    • Nikolaos Karalis
    • , Cyril Dejean
    • , Fabrice Chaudun
    • , Suzana Khoder
    • , Robert R Rozeske
    • , Hélène Wurtz
    • , Julien Courtin
    •  & Cyril Herry
  2. Univ. Bordeaux, Neurocentre Magendie, U862, Bordeaux, France.

    • Nikolaos Karalis
    • , Cyril Dejean
    • , Fabrice Chaudun
    • , Suzana Khoder
    • , Robert R Rozeske
    • , Hélène Wurtz
    • , Julien Courtin
    •  & Cyril Herry
  3. Bernstein Center for Computational Neuroscience Munich, Munich Cluster of Systems Neurology (SyNergy), Faculty of Medicine, Ludwig-Maximilians Universität München, Planegg-Martinsried, Germany.

    • Nikolaos Karalis
    •  & Anton Sirota
  4. Team Memory, Oscillations and Brain states (MOBs), Brain Plasticity Unit, CNRS UMR 8249, ESPCI ParisTech, Ecole Supérieure de Physique et de Chimie Industrielles de la Ville de Paris, Paris, France.

    • Sophie Bagur
    •  & Karim Benchenane
  5. Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.

    • Julien Courtin

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Contributions

S.B., K.B., F.C., J.C., C.D., N.K., S.K., R.R.R., A.S. and H.W. performed the experiments and analyzed the data. J.C., C.D., N.K. and C.H. designed the experiments. C.H. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Nikolaos Karalis or Cyril Herry.

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DOI

https://doi.org/10.1038/nn.4251

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