Fig. 3.

SFO-IL-1R1 signaling modulates delated effects of CO₂ on active and passive behaviors during contextual fear conditioning, extinction and reinstatement. Top panel shows the layout of the fear conditioning paradigm. See Fig. 1 for full experimental layout (mice received SFO-targeted infusions of IL-1RA or vehicle 30 min prior to CO₂ or air exposure a week prior to fear conditioning). A) On fear acquisition day, SFO-IL-1RA infusion one week earlier significantly reduced freezing following foot shocks only in mice previously exposed to CO₂ inhalation. No significant treatment effects were observed in air-exposed mice. B) In response to foot shock, prior IL-1RA treatment increased rearing in previously CO₂– exposed mice, but not air- exposed mice. C) Prior IL-1RA treatment attenuated conditioned freezing 24 h post-shock in previously CO₂– exposed mice, but not air- exposed mice. D) Prior IL-1RA treatment also attenuated the heightened freezing during extinction in CO₂-exposed mice, with no effects in air- exposed mice. Additionally, prior IL-1RA treatment attenuated freezing responses (E) and increased rearing responses (F) to a reminder foot shock during fear reinstatement only in mice previously exposed to CO₂ inhalation. Data are mean ± SEM. CO₂/VEH vs CO₂/IL-1RA: *p < 0.05 **p < 0.01; CO₂/VEH vs Air/VEH: ^p < 0.05 ^^p < 0.01; CO₂/VEH vs Air/IL-1RA: ^#p < 0.05 ^##p < 0.01; Air/IL-1RA vs CO₂/IL-1RA: ^&p < 0.05; Air/VEH vs CO₂/IL-1RA: ^%p < 0.05. (n = 9–13) H = Habituation, S = Shock 1, 2, or 3, E = Extinction Day.