Defense is a basic survival mechanism when animals face danger. Previous studies have suggested that the midbrain periaqueductal gray (PAG) is essential for the generation of defensive reactions. Here we showed that optogenetic activation of neurons in the PAG in mice was sufficient to induce a series of defensive responses (including running, freezing, and avoidance). However, the endogenous neural dynamics of the PAG underlying defensive behaviors still remain elusive. Using chronic extracellular recording, we recorded the spiking activities of PAG neurons in freely behaving mice exposed to natural threats (rats). We observed that there exist distinct neuronal subsets within the PAG participating in respective detection (risk assessment) and response (flight) aspects of defensive behaviors. Our results demonstrate the important role of PAG neuronal activities in the control of different aspects of defensive behaviors, and provide novel insights for investigating defense from an electrophysiological perspective.

Highlights d Tshz1 labels a population of striatal direct pathway medium spiny neurons (dMSNs) d Tshz1-expressing (Tshz1 + ) dMSNs are localized in the striosome d Tshz1 + striosomal dMSNs represent punishment and drive negative reinforcement d Pdyn labels another population of striosomal dMSNs mediating positive reinforcement