Midbrain circuits for defensive behaviour

Philip Tovote, Maria Soledad Esposito, Paolo Botta, Fabrice Chaudun, Jonathan P. Fadok, Milica Markovic, Steffen B. E. Wolff, Charu Ramakrishnan, Lief Fenno, Karl Deisseroth, Cyril Herry, Silvia Arber, Andreas Lüthi
Nature. 2016-06-01; 534(7606): 206-212
DOI: 10.1038/nature17996

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

Midbrain circuits for defensive behaviour.

Tovote P(1), Esposito MS(1)(2), Botta P(1), Chaudun F(3), Fadok JP(1), Markovic
M(1), Wolff SB(1), Ramakrishnan C(4), Fenno L(4), Deisseroth K(4), Herry C(3),
Arber S(1)(2), Lüthi A(1).

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.

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.

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


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