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.
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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.
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Ciocchi, S., Herry, C., Grenier, F. et al. Encoding of conditioned fear in central amygdala inhibitory circuits. Nature 468, 277–282 (2010). https://doi.org/10.1038/nature09559
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DOI: https://doi.org/10.1038/nature09559
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