Fig. 1: Long-lasting alterations of behavior after trauma and its association with the estrous cycle phase.

a Schematic representation of the behavioral protocol. b Fear learning and fear extinction in naturally cycling females undergoing IMO or compensatory handling (control: n = 31, IMO: n = 32) (P = 0.001). c Methods used to monitor the estrous cycle before the behavioral procedures. d Estrous cycle and related hormonal levels in female C57BL/6 mice. e Fear learning, and fear extinction in proestrus or metestrus females (n = 7 per group) (P = 0.029). Data are expressed as mean ± SEM. *P ≤ 0.05, ***P ≤ 0.001. In b, e, main effect stress, main effect estrous cycle, main effect FE session or CS, and FE session* stress or CS*stress, estrous cycle*stress, FE session * estrous cycle, FE session * stress * estrous cycle interactions were analyzed using repeated-measures ANOVA, Bonferroni corrections were made for multiple comparisons. Asterisks above a line indicate significant main effect stress in repeated-measures ANOVA. CS conditioned stimulus, D diestrus, E estrus, FC fear conditioning, FE fear extinction session, IMO immobilization stress, M metestrus, Met metestrus, P proestrus, Pro proestrus. Source data are provided as a Source Data file.