Animals faced with predatorial threats innately react by escaping to safety. Although escape is instinctive, it is also flexible enough to adapt to dynamic changes in the environment. For example, animals adapt to the risk of predation by increasing escape probability when there is a higher incidence of predator attacks. This flexibility is critical for maximizing the adaptiveness of behavioural choices, but the underlying mechanisms are unknown. Previous work has shown that activation of neurons in the dorsal periaqueductal gray (dPAG) is the main step for commanding escape initiation. Here we hypothesized that changing the excitability of dPAG neurons is a mechanism for implementing experience-dependent adaptations of escape behavior. We developed a new paradigm of head-restrained mice who navigate between a shelter and a threat zone and are exposed to threatening stimuli that cause escape responses. To modulate escape, we presented repeated stimuli, which caused an increase in the probability and vigour of escape, indicating a decrease in the escape threshold. Using whole-cell recordings from dPAG neurons we studied the cellular mechanisms of escape threshold modulation and found that repeated presentation of escape-eliciting stimuli causes a subthreshold sustained depolarization that lasts for several minutes. This depolarization reduces the amount of synaptic input needed to reach action potential threshold. Consequently, subsequent threatening stimuli are more likely to elicit action potentials and therefore escape initiation. We further show that the sustained depolarization arises from a local disinhibitory mechanism. Our findings present a cellular mechanism for rapid experience-dependent modulation of instinctive escape behaviour.