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Anxiety is presumably driven by fear memory. Molecular profiles in the amygdala of mice with fear memory induced by psychological and physical stresses remain to be elucidated. Fear memory in mice was induced by a paradigm of social defeat. Physical and psychological stresses (PPS) to an intruder were given by attacks from an aggressive resident. Psychological stress (PS) to an observer was given by the witnessing of aggressor attacks. Amygdala tissues from these mice showing fear memory and anxiety vs. tissues from control mice were harvested to analyze mRNA and microRNA profiles by high-throughput sequencing. In the amygdala of intruders and observers with fear memory, the genes encoding 5-HTR1b, 5-HTR2a, DAR2, AChRM3, and IP3R1 are upregulated, whereas genes encoding GPγ11, GPγ13, GPγT2, RasC3, and P450 are downregulated, indicating that these molecules are involved in fear memory induced by physical/psychological stresses. In the comparison of intruders with observers, the upregulation of genes encoding 5-HTR6, GPγ8, P2R7, NFκ2, CREB3/1, and Itgα9 as well as the downregulation of genes encoding DAR5, 5-HTR1a, and HSP1a are involved in fear memory induced by physical stress. The upregulation of genes encoding DAR1, 5-HTR5a and SSR2/3 as well as the downregulation of AdRα1, CREB3/1, GPγ13 and GPγ8 are involved in fear memory induced by psychological stress. Results obtained by sequencing mRNA and microRNA profiles are consistent with results of quantitative RT-PCR analysis and dual-luciferase reporter assays performed for validation. In conclusion, fear memories and anxiety induced by PPS vs. PS are caused by the imbalanced regulation of different synapses and signaling pathways in the amygdala.    NEW &amp; NOTEWORTHY The current study identifies the molecular mechanism underlying fear memory and anxiety induced by psychological stress vs. physical stress, in which the imbalanced expression of microRNA-regulated mRNAs relevant to dopaminergic, adrenergic, and serotonergic synapses in the amygdala plays an important role. This result reveals different molecular profiles for psychological and physical stresses.

microRNA and mRNA profiles in the amygdala are relevant to fear memory induced by physical or psychological stress