Fig. 3: Post-trauma operant training facilitates the reduction of generalized fear in vulnerable subjects.

A Schematic representation of the design of Experiment #4 with trauma exposure, brief fear recall testing in traumatic (CtxA, 5 min) and safe (CtxB, 10 min) contexts before operant training (complex task as used in Experiment #3), that was followed again by fear recall testing in CtxA and B. B Pre-training generalized fear responses were carefully counterbalanced between trained and yoked control subgroups within both resilient and vulnerable subpopulations (p > 0.720). C Following operant training intervention, generalized fear responses remained significantly elevated in the vulnerable group compared to resilient counterparts. D Vulnerable subjects that received operant training exhibited significantly accelerated reduction of generalized fear compared to yoked subjects (p = 0.047), indicating a training-specific therapeutic effect. This was not apparent in the resilient group (p = 0.859), likely due to a floor effect in this population E Volcano plots depicting differentially expressed genes in the medial prefrontal cortex (mPFC) and F hippocampus (HPC) following operant training intervention relative to yoked controls in both vulnerable and resilient groups. Genes meeting significance thresholds (p < 0.05, indicated by blue horizontal line) with biologically relevant expression changes (>1.2-fold, indicated by vertical dashed lines) are highlighted. Significantly upregulated genes are denoted in red and downregulated genes in green. Key plasticity-related genes identified including, Bcan (brevican), Igf1 (insulin-like growth factor 1), Nlgn1 (Neuroligin 1), Nrxn1 (Neurexin 1), Rtn4r (Nogo receptor), Grm1 (metabotropic glutamate receptor 1), besides others such as Fos, Crh (corticotropin releasing hormone), Maoa and Maob (monoamine oxidase A and B). All data are presented as mean ± SEM. *p < 0.05, ***p < 0.001; Two-way ANOVA with Tukey’s post hoc test, or repeated measures ANOVA.