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Encoding of conditioned fear in central amygdala inhibitory circuits

Nature volume 468, pages 277282 (11 November 2010) | Download Citation

Abstract

The central amygdala (CEA), a nucleus predominantly composed of GABAergic inhibitory neurons, is essential for fear conditioning. How the acquisition and expression of conditioned fear are encoded within CEA inhibitory circuits is not understood. Using in vivo electrophysiological, optogenetic and pharmacological approaches in mice, we show that neuronal activity in the lateral subdivision of the central amygdala (CEl) is required for fear acquisition, whereas conditioned fear responses are driven by output neurons in the medial subdivision (CEm). Functional circuit analysis revealed that inhibitory CEA microcircuits are highly organized and that cell-type-specific plasticity of phasic and tonic activity in the CEl to CEm pathway may gate fear expression and regulate fear generalization. Our results define the functional architecture of CEA microcircuits and their role in the acquisition and regulation of conditioned fear behaviour.

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Acknowledgements

We thank all members of the Lüthi laboratory for discussions and critical comments on the manuscript. This work was supported by grants from the Austrian Science Fund (FWF), the Swiss National Science Foundation, the Schering Foundation, the European Commission (Eurospin Project, Contract HEALTH-F2-2009-241498), the Indo Swiss Joint Research Programme, the BMBF (grant 01GQ0420 to BCCN Freiburg), Neurex Interreg-IV, the Volkswagen Stiftung, the Novartis Institutes for Biomedical Research, and the Novartis Research Foundation.

Author information

Author notes

    • Stephane Ciocchi
    •  & Cyril Herry

    These authors contributed equally to this work.

    • Cyril Herry
    •  & Ingrid Ehrlich

    Present addresses: INSERM U862, Neurocentre Magendie, 146 Rue Léo-Saignat, 33077 Bordeaux, France (C.H.); Hertie Institute for Clinical Brain Research, 72076 Tübingen, Germany (I.E.).

Affiliations

  1. Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland

    • Stephane Ciocchi
    • , Cyril Herry
    • , François Grenier
    • , Steffen B. E. Wolff
    • , Johannes J. Letzkus
    • , Ingrid Ehrlich
    • , Michael B. Stadler
    • , Christian Müller
    •  & Andreas Lüthi
  2. Bernstein Center for Computational Neuroscience, 79104 Freiburg, Germany

    • Ioannis Vlachos
  3. Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany

    • Rolf Sprengel
  4. Department of Bioengineering, Stanford University, Stanford, California 94305, USA

    • Karl Deisseroth

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Contributions

S.C. and C.H. initiated the project. S.C., C.H., F.G., S.B.E.W. and C.M. performed the experiments. S.C., C.H., F.G., S.B.E.W., I.V., M.B.S. and A.L. analysed the data. K.D. and R.S. provided constructs and advice. S.C., C.H., F.G., S.B.E.W., I.E. and J.J.L. contributed to the experimental design and interpretation. A.L. conceived the project, contributed to the experimental design and interpretation, analysed data and wrote the manuscript. S.C. and C.H. contributed equally. All authors discussed the results and commented on the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Andreas Lüthi.

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    Supplementary Information

    This file contains Supplementary Notes, an additional reference and Supplementary Figures 1-16 with legends.

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DOI

https://doi.org/10.1038/nature09559

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