Threat history controls flexible escape behavior in mice

In many instances, external sensory-evoked neuronal activity is used by the brain to select the most appropriate behavioral response. Predator-avoidance behaviors such as freezing and escape(1)(,)(2) are of particular interest since these stimulus-evoked responses are behavioral manifestations of a decision-making process that is fundamental to survival.(3)(,)(4) Over the lifespan of an individual, however, the threat value of agents in the environment is believed to undergo constant revision,(5) and in some cases, repeated avoidance of certain stimuli may no longer be an optimal behavioral strategy.(6) To begin to study this type of adaptive control of decision-making, we devised an experimental paradigm to probe the properties of threat escape in the laboratory mouse Mus musculus. First, we found that while robust escape to visual looming stimuli can be observed after 2 days of social isolation, mice can also rapidly learn that such stimuli are non-threatening. This learned suppression of escape (LSE) is extremely robust and can persist for weeks and is not a generalized adaptation, since flight responses to novel live prey and auditory threat stimuli in the same environmental context were maintained. We also show that LSE cannot be explained by trial number or a simple form of stimulus desensitization since it is dependent on threat-escape history. We propose that the action selection process mediating escape behavior is constantly updated by recent threat history and that LSE can be used as a robust model system to understand the neurophysiological mechanisms underlying experience-dependent decision-making.