LAUSR

Significance Mice evaluate interaction with conspecifics by their potential for harm or benefit. Similarly, the ability to discriminate social stimuli is of fundamental importance in humans: A delicate balance between fear response generalization and discrimination can promote resilience in an ever-changing world. Here, we establish a translationally informed approach to detect resilience versus susceptibility to social defeat stress. We capitalize on the individual ability of mice to discriminate between threat and safe stimuli under stressful conditions, and their response to extinction. We identify a behavioral phenotype of resilience supported by unique transcriptional signatures in specific nuclei of the fear circuitry. Our approach might serve as a blueprint for advancing the development of prevention strategies against stress-related mental disorders.