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Nature. 2016 Jun 9;534(7606):206-12. doi: 10.1038/nature17996. Epub 2016 Jun 1.

Midbrain circuits for defensive behaviour.

Author information

1
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
2
Biozentrum, Department of Cell Biology, University of Basel, 4056 Basel, Switzerland.
3
INSERM, Neurocentre Magendie, U862, 146 Rue Léo-Saignat, Bordeaux 33077, France.
4
Stanford University, 318 Campus Drive West, Clark Center W080, Stanford, California 94305, USA.

Abstract

Survival in threatening situations depends on the selection and rapid execution of an appropriate active or passive defensive response, yet the underlying brain circuitry is not understood. Here we use circuit-based optogenetic, in vivo and in vitro electrophysiological, and neuroanatomical tracing methods to define midbrain periaqueductal grey circuits for specific defensive behaviours. We identify an inhibitory pathway from the central nucleus of the amygdala to the ventrolateral periaqueductal grey that produces freezing by disinhibition of ventrolateral periaqueductal grey excitatory outputs to pre-motor targets in the magnocellular nucleus of the medulla. In addition, we provide evidence for anatomical and functional interaction of this freezing pathway with long-range and local circuits mediating flight. Our data define the neuronal circuitry underlying the execution of freezing, an evolutionarily conserved defensive behaviour, which is expressed by many species including fish, rodents and primates. In humans, dysregulation of this 'survival circuit' has been implicated in anxiety-related disorders.

PMID:
27279213
DOI:
10.1038/nature17996
[Indexed for MEDLINE]
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