A Biophysical Mechanism for Changing the Threat Sensitivity of Escape Behavior

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. It has recently been 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.

To investigate this hypothesis, we developed a new paradigm for performing whole-cell recordings from dPAG neurons of mice escaping from threatening stimuli. Head-restrained mice navigate between a shelter and a threat zone and are exposed to threatening stimuli that cause escape-to-shelter responses. To modulate escape behavior we presented repeated stimuli, which caused an increase in the probability and vigor of escape, indicating a decrease in the escape threshold. Using this sensitization paradigm and whole-cell recordings we studied the cellular mechanisms of escape threshold modulation. We found that repeated presentation of escape-eliciting stimuli causes a subthreshold sustained depolarization that lasts for several minutes. This depolarization is large enough to reduce the amount of synaptic input needed to reach the action potential threshold. Consequently, subsequent threatening stimuli are more likely to elicit action potentials and therefore escape initiation. We further propose that the sustained depolarization arises from a local disinhibitory mechanism. Our findings present a cellular mechanism for rapid experience-dependent modulation of instinctive escape behavior. We suggest that this biophysical process at the level of single midbrain neurons may be a general mechanism for modulating behavior initiation in dynamic environments.