Rapid Spatial Learning Controls Instinctive Defensive Behavior in Mice

Instinctive defensive behaviors are essential for animal survival. Across the animal kingdom, there are sensory stimuli that innately represent threat and trigger stereotyped behaviors such as escape or freezing [1–4]. While innate behaviors are considered to be hard-wired stimulus-responses [5], they act within dynamic environments, and factors such as the properties of the threat [6–9] and its perceived intensity [1, 10, 11], access to food sources [12–14], and expectations from past experience [15, 16] have been shown to influence defensive behaviors, suggesting that their expression can be modulated. However, despite recent work [2, 4, 17–21], little is known about how flexible mouse innate defensive behaviors are and how quickly they can be modified by experience. To address this, we have investigated the dependence of escape behavior on learned knowledge about the spatial environment and how the behavior is updated when the environment changes acutely. Using behavioral assays with innately threatening visual and auditory stimuli, we show that the primary goal of escape in mice is to reach a previously memorized shelter location. Memory of the escape target can be formed in a single shelter visit lasting less than 20 s, and changes in the spatial environment lead to a rapid update of the defensive action, including changing the defensive strategy from escape to freezing. Our results show that although there are innate links between specific sensory features and defensive behavior, instinctive defensive actions are surprisingly flexible and can be rapidly updated by experience to adapt to changing spatial environments. •Mice instinctively escape to a previously memorized shelter location•Orientation and navigation to the shelter does not require shelter-related cues•Memory of the shelter location is formed in a single trial•Changes in the spatial environment lead to rapid updates of defensive actions Vale et al. show that mice exposed to innately aversive stimuli instinctively escape to a shelter location that was learned during exploration of the environment. Memory of shelter existence and location is formed in a single trial and can be rapidly updated, allowing mice to quickly adapt defensive actions to changes in the spatial environment.