Decoding the language of fear: Unveiling objective and subjective indicators in rodent models through a systematic review and meta-analysis

While rodent models are vital for studying mental disorders, the underestimation of construct validity of fear indicators has led to limitations in translating to effective clinical treatments. Addressing this gap, we systematically reviewed 5054 articles from the 1960 s, understanding underlying theoretical advancement, and selected 68 articles with at least two fear indicators for a three-level meta-analysis. We hypothesized correlations between different indicators would elucidate similar functions, while magnitude differences could reveal distinct neural or behavioral mechanisms. Our findings reveal a shift towards using freezing behavior as the primary fear indicator in rodent models, and strong, moderate, and weak correlations between freezing and conditioned suppression ratios, 22-kHz ultrasonic vocalizations, and autonomic nervous system responses, respectively. Using freezing as a reference, moderator analysis shows treatment types and fear stages significantly influenced differences in magnitudes between two indicators. Our analysis supports a two-system model of fear in rodents, where objective and subjective fears could operate on a threshold-based mechanism.