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 and Andreas Lüthi ()
Additional contact information
Philip Tovote: Friedrich Miescher Institute for Biomedical Research
Maria Soledad Esposito: Friedrich Miescher Institute for Biomedical Research
Paolo Botta: Friedrich Miescher Institute for Biomedical Research
Fabrice Chaudun: INSERM, Neurocentre Magendie, U862
Jonathan P. Fadok: Friedrich Miescher Institute for Biomedical Research
Milica Markovic: Friedrich Miescher Institute for Biomedical Research
Steffen B. E. Wolff: Friedrich Miescher Institute for Biomedical Research
Charu Ramakrishnan: Stanford University, 318 Campus Drive West
Lief Fenno: Stanford University, 318 Campus Drive West
Karl Deisseroth: Stanford University, 318 Campus Drive West
Cyril Herry: INSERM, Neurocentre Magendie, U862
Silvia Arber: Friedrich Miescher Institute for Biomedical Research
Andreas Lüthi: Friedrich Miescher Institute for Biomedical Research

Nature, 2016, vol. 534, issue 7606, 206-212

Abstract: 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.

Date: 2016
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DOI: 10.1038/nature17996

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