Midbrain circuits for defensive behaviour

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / cytology
  • Amygdala / physiology
  • Animals
  • Escape Reaction / physiology*
  • Freezing Reaction, Cataleptic / physiology*
  • GABAergic Neurons / physiology
  • Glutamic Acid / metabolism
  • Male
  • Medulla Oblongata / cytology
  • Medulla Oblongata / physiology
  • Mice
  • Mice, Inbred C57BL
  • Neural Inhibition / physiology
  • Neural Pathways / cytology*
  • Neural Pathways / physiology*
  • Neuroanatomical Tract-Tracing Techniques
  • Optogenetics
  • Periaqueductal Gray / cytology*
  • Periaqueductal Gray / physiology*

Substances

  • Glutamic Acid