Contextual modulation and blunted defensive responses to predators in head-fixed and freely moving mice

Behavioral responses to threat -- such as fleeing, freezing, or fighting--can be innate, learned, and strongly shaped by context or competing goals. Here, we asked whether exposure to an ecologically relevant predator obligatorily elicits canonical defensive behaviors across behavioral contexts. We examined predator responses in mice across four experimental conditions: one novel head-fixed reward-driven foraging task and three established paradigms in freely moving animals. In the head-fixed condition, water-deprived mice were trained to walk on a treadmill controlling a virtual environment and water reward delivery and were subsequently exposed to a live rat positioned above the lick spout. Despite the presence of the predator, most mice (5 of 7) maintained foraging performance at baseline levels. However, individual mice exhibited significant, coordinated changes in running speed, pupil diameter, eye movements, and posture, indicating engagement with the threat. To assess how context influences predator responses, we exposed 36 naive, freely moving mice to fear-inducing stimuli, including looming visual cues, rat odor, and a live rat. Even under these conditions, defensive behaviors were variable: only a subset of mice displayed avoidance or escape, and when presented with a freely moving rat, approximately half of the mice avoided the predator. Together, these findings show that predator threat does not elicit a uniform or obligatory defensive repertoire in mice. Instead, defensive responses are expressed flexibly, and are shaped by environmental constraints, task demands, and individual variability. These results challenge the assumption that innate fear behaviors are automatically triggered by predator encounters. Graphical AbstractUsing a head-fixed, reward-based foraging task and complementary freely moving paradigms, we show that mouse responses to predator-related stimuli are variable and context dependent, with limited expression of canonical defensive behaviors such as freezing or flight. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/658679v3_ufig1.gif" ALT="Figure 1"> View larger version (65K): org.highwire.dtl.DTLVardef@1fa4570org.highwire.dtl.DTLVardef@1e4c33borg.highwire.dtl.DTLVardef@1cd6bf9org.highwire.dtl.DTLVardef@16bdeb3_HPS_FORMAT_FIGEXP M_FIG C_FIG