CALIBRATION OF MOUSE DEFENSIVE BEHAVIORS ACROSS DANGER STATES AND THEIR NEURAL CORRELATES

Animals rely on conserved defensive behaviors that integrate spatial and temporal information, prior experience, and internal states to evaluate danger along the threat imminence continuum. Distributed neural circuits are thought to support different defensive strategies across danger states, and dysfunction within these pathways may contribute to maladaptive threat processing in fear and anxiety disorders. Studying this continuum is challenging because it requires quantifying multivariate defensive behaviors under dynamically changing threat conditions.
To address this, we repurposed the active place avoidance paradigm and developed an analytical pipeline that tracks animal pose and translates movement into discrete behavioral motifs, including avoidance, freezing, risk assessment, darting, and escape, across potential, acute, and immediate danger states. Brain-wide activity mapping revealed distinct and overlapping neural networks associated with behavioral output, salience, and danger level, highlighting a key role for midbrain circuitry in risk assessment.
We then used chemogenetic and optogenetic manipulations to examine the contribution of ventral tegmental area dopamine neurons to defensive behavior selection. Our findings indicate that dopamine activity biases behavior toward risk assessment over freezing during acute threat, influenced by the degree of agency animals exert over danger. Ongoing fiber photometry studies examine downstream dopamine-sensitive pathways across striatal territories in freely moving animals across danger states.
Together this work aims to link circuit-level dynamics with behavior, refining models of threat imminence processing, and providing a framework for understanding individual variability and maladaptive defensive strategies across danger states.