Fig. 3
Alprazolam alters dorsal hippocampal ensembles and engrams in female but not male mice. (A) ArcCreERT2 x EYFP genetic model and ensemble tagging. (B) CFC timeline for ensemble tagging. (C) Alprazolam treated ArcCreERT2 x EYFP show similar levels of freezing compared to other timelines during CFC training (D) Alprazolam treated ArcCreERT2 x EYFP mice show significantly less freezing during re-exposure compared to saline treated controls. (E,F). Alprazolam and saline treated male mice show comparable encoding and retrieval ensemble activation in the dorsal hippocampus. (G,H) Alprazolam and saline treated male mice show comparable engram activation when compared to encoding or retrieval ensembles. (I,J) Representative images of tagged ensembles in saline and alprazolam treated male mice. (K) Alprazolam treated female mice show significantly greater encoding ensemble activation in the dorsal CA1 of the hippocampus. (L) Alprazolam and saline treated female mice show comparable retrieval ensemble activation in the dorsal hippocampus. (M) Alprazolam and saline treated female mice show comparable engram activation in the dorsal hippocampus with overlap compared to encoding ensembles. (N) Alprazolam treated female mice show significantly greater engram activation in the dorsal CA3 of the hippocampus when overlap is compared to retrieval ensembles. (O,P) Representative images of tagged ensembles in saline and alprazolam treated female mice. White arrows indicate overlap cells. (n = 5 mice per group). Error bars represent ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001; 4-OHT, 4-hydroxytamoxifen; dDG, dorsal dentate gyrus; dCA3, dorsal cornu ammonis 3; dCA1, dorsal cornu ammonis 1; Alp, alprazolam; mg, milligram; kg, kilogram; sal, saline; CFC, contextual fear conditioning.
