Midbrain circuits for defensive behaviour.
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.
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Philip
P
Tovote
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.|Biozentrum, Department of Cell Biology, University of Basel, 4056 Basel, Switzerland.
Maria Soledad
MS
Esposito
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Paolo
P
Botta
INSERM, Neurocentre Magendie, U862, 146 Rue Léo-Saignat, Bordeaux 33077, France.
Fabrice
F
Chaudun
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Jonathan P
JP
Fadok
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Milica
M
Markovic
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Steffen B E
SB
Wolff
Stanford University, 318 Campus Drive West, Clark Center W080, Stanford, California 94305, USA.
Charu
C
Ramakrishnan
Stanford University, 318 Campus Drive West, Clark Center W080, Stanford, California 94305, USA.
Lief
L
Fenno
Stanford University, 318 Campus Drive West, Clark Center W080, Stanford, California 94305, USA.
Karl
K
Deisseroth
INSERM, Neurocentre Magendie, U862, 146 Rue Léo-Saignat, Bordeaux 33077, France.
Cyril
C
Herry
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.|Biozentrum, Department of Cell Biology, University of Basel, 4056 Basel, Switzerland.
Silvia
S
Arber
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Andreas
A
Lüthi
D000679:Amygdala / Q000166:cytology / Q000502:physiology; D000818:Animals; D004924:Escape Reaction / Q000502:physiology*; D046352:Freezing Reaction, Cataleptic / Q000502:physiology*; D059330:GABAergic Neurons / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000502:physiology; D009434:Neural Pathways / Q000166:cytology* / Q000502:physiology*; D056347:Neuroanatomical Tract-Tracing Techniques; D062308:Optogenetics; D010487:Periaqueductal Gray / Q000166:cytology* / Q000502:physiology*
D018698:Glutamic Acid