Philip Tovote (Friedrich Miescher Institute for Biomedical Research, Basel) | Midbrain circuits for defensive behavior

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. We used circuit-based optogenetic, in vivo and in vitro electrophysiological, and neuroanatomical tracing methods to define midbrain periaqueductal grey (PAG) circuits for specific defensive behaviors. We identified an inhibitory pathway from the central nucleus of the amygdala (CEA) to the ventrolateral PAG (vlPAG) that produces freezing by disinhibition of vlPAG 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 evolutionary conserved defensive behavior, 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.