Tonically active GABAergic neurons in the dorsal periaqueductal gray control the initiation and execution of instinctive escape

To avoid predation, animals perform defensive actions that are both instinctive and adaptable to the environment. In mice, the decision to escape from imminent threats is implemented by a feed-forward circuit in the midbrain, where excitatory VGluT2+ neurons in the dorsal periaqueductal gray (dPAG) compute escape initiation and escape vigour from threat evidence. Here we show that GABAergic VGAT+ neurons in the dPAG dynamically control this process by modulating the excitability of excitatory escape neurons. Using in vitro patchclamp and in vivo neural activity recordings in freely behaving mice we found that VGAT+ dPAG neurons fire action potentials tonically in the absence of synaptic inputs and are a major source of synaptic inhibition to VGluT2+ dPAG neurons. Activity in these spontaneously firing VGAT+ cells transiently decreases at escape onset and increases during escape, peaking at escape termination. Optogenetically increasing or decreasing VGAT+ dPAG activity bidirectionally changes the probability of escape when the stimulation is delivered at the time of threat onset, and the duration of escape when delivered after escape initiation. We conclude that the activity of tonically firing VGAT+ dPAG neurons sets a threshold for escape initiation and controls the execution of the flight locomotor action.