Fig. 2. The IL-PFC exhibits robust IEG induction and IEG-mediated cellular tagging following social interaction.

a Representative images of c-fos induction following exposure to a novel or familiar mouse, compared with controls exposed to a novel object (conical tube). Scale bars left = 10 mm, right = 50 µm. b Quantification of c-fos⁺ cells in mice exposed to a novel object (n = 3), a novel mouse (n = 6), or a familiar mouse (n = 4). Exposure to a novel or familiar mouse results in significant induction of c-fos⁺ cells relative to object-exposed controls, but there were no differences between socially exposed groups (p = 0.098). c ArcCreER^T2 × Rosa^ChR2-eYFP mice were used to indelibly label socially active neurons with ChR2-eYFP. Briefly, CreER^T2 is under the control of the Arc promoter. Upon administration of 4-OHT, CreER^T2 localizes to the nucleus and recombines loxP sites in the floxed-STOP-ChR2-eYFP transgene, resulting in indelible expression of ChR2-eYFP in Arc⁺ cells. Labeling ends when 4-OHT is metabolized and excreted. d Timeline for labeling a social neural ensemble in the IL-PFC. Mice received 4-OHT or vehicle and 5 h later were exposed to a new cagemate or novel object. e Representative images of immunolabeling of ChR2-eYFP⁺ cells in the IL-PFC in mice receiving 4-OHT or vehicle prior to exposure to a novel mouse or a novel object. Scale bars = 50 µm. f Quantification of eYFP in the IL-PFC, where robust labeling was observed in mice receiving 4-OHT and exposed to a novel mouse compared with an object or vehicle controls (n = 8 mice per group). Error bars represent ± SEM. *p < 0.05; **p < 0.01, ***p < 0.001. Veh, vehicle; 4-OHT, 4-hydroxytamoxifen; stim, stimulus; sac, sacrifice; norm, normalized.