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Switching on and off fear by distinct neuronal circuits

Abstract

Switching between exploratory and defensive behaviour is fundamental to survival of many animals, but how this transition is achieved by specific neuronal circuits is not known. Here, using the converse behavioural states of fear extinction and its context-dependent renewal as a model in mice, we show that bi-directional transitions between states of high and low fear are triggered by a rapid switch in the balance of activity between two distinct populations of basal amygdala neurons. These two populations are integrated into discrete neuronal circuits differentially connected with the hippocampus and the medial prefrontal cortex. Targeted and reversible neuronal inactivation of the basal amygdala prevents behavioural changes without affecting memory or expression of behaviour. Our findings indicate that switching between distinct behavioural states can be triggered by selective activation of specific neuronal circuits integrating sensory and contextual information. These observations provide a new framework for understanding context-dependent changes of fear behaviour.

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Figure 1: Distinct populations of BA neurons encode fear conditioning and extinction.
Figure 2: Fear and extinction neurons discriminate stimuli with different emotional significance.
Figure 3: Sequential switches in neuronal activity precede behavioural changes.
Figure 4: Context-dependent fear renewal induces rapid reversal of neuronal activity patterns.
Figure 5: Fear neurons and extinction neurons are part of distinct neuronal circuits.
Figure 6: Targeted inactivation of the BA prevents behavioural changes without affecting memory.

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Acknowledgements

We thank R. Friedrich, A. Matus and all members of the Lüthi laboratory for discussions and critical comments on the manuscript and E. Oakeley and M. Stadler for advice on statistical analysis and programming. This work was supported by the Austrian Science Fund (FWF), the Novartis Institutes for Biomedical Research, and the Novartis Research Foundation.

Author Contributions C.H., S.C., V.S., L.D. and C.M. performed the experiments and analysed the data. C.H., S.C. and A.L. designed the experiments and wrote the paper.

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Correspondence to Cyril Herry or Andreas Lüthi.

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Herry, C., Ciocchi, S., Senn, V. et al. Switching on and off fear by distinct neuronal circuits. Nature 454, 600–606 (2008). https://doi.org/10.1038/nature07166

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