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The central nucleus of the amygdala and the construction of defensive modes across the threat-imminence continuum

Abstract

In nature, animals display defensive behaviors that reflect the spatiotemporal distance of threats. Laboratory-based paradigms that elicit specific defensive responses in rodents have provided valuable insight into the brain mechanisms that mediate the construction of defensive modes with varying degrees of threat imminence. In this Review, we discuss accumulating evidence that the central nucleus of the amygdala (CeA) plays a key role in this process. Specifically, we propose that the mutually inhibitory circuits of the CeA use a winner-takes-all strategy that supports transitioning across defensive modes and the execution of specific defensive behaviors to previously formed threat associations. Our proposal provides a conceptual framework in which seemingly divergent observations regarding CeA function can be interpreted and identifies various areas of priority for future research.

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Fig. 1: CeA construct defensive modes through a winner-takes-all mechanism.
Fig. 2: Laboratory tasks for studying defensive behaviors across the various stages of threat imminence.
Fig. 3: Neuromodulation in the CeA impacts the construction of defensive modes.

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Acknowledgements

This work was supported by the NIMH Intramural Research Program (1ZIAMH002950 to M.A.P.). We thank C. Cain and F. Do Monte for providing critical comments on the manuscript.

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Correspondence to Justin M. Moscarello or Mario A. Penzo.

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Nature Neuroscience thanks Michael Fanselow, Sabine Krabbe, and Pankaj Sah for their contribution to the peer review of this work.

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Moscarello, J.M., Penzo, M.A. The central nucleus of the amygdala and the construction of defensive modes across the threat-imminence continuum. Nat Neurosci 25, 999–1008 (2022). https://doi.org/10.1038/s41593-022-01130-5

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