Traumatic stress induces prolonged aggression increase through synaptic potentiation in the medial amygdala circuits
Traumatic stress can lead to heightened aggression which may be a symptom of psychiatric diseases such as PTSD and intermittent explosive disorder. The medial amygdala (MeA) is an evolutionarily conserved subnucleus of the amygdala that regulates attack behavior and behavioral responses to stressors. The precise contribution of the MeA in traumatic stress-induced aggression, however, requires further elucidation. In this study, we used foot shock to induce traumatic stress in mice and examine the mechanisms of prolonged aggression increase associated with it. Foot shock causes a prolonged increase in aggression that lasts at least one week. In vivo electrophysiological recordings revealed that foot shock induces potentiation of synapses formed between the MeA and the ventromedial hypothalamus (VmH) and bed nucleus of the stria terminalis (BNST). This synaptic potentiation lasts at least one week. Induction of synaptic depotentiation with low-frequency photostimulation (LFPS) immediately after foot shock suppresses the prolonged aggression increase without affecting non-aggressive social behavior, anxiety-like and depression-like behaviors, or fear learning. These results show that potentiation of the MeA-VmH and MeA-BNST circuits is essential for traumatic stress to cause a prolonged increase in aggression. These circuits may be potential targets for the development of therapeutic strategies to treat the aggression symptom associated with psychiatric diseases.
SIGNIFICANCE STATEMENT Heightened aggression can be a blight on society and a symptom of many psychiatric diseases. In this study we show that traumatic stress produces an enhancement of aggression that lasts at least one week through potentiation of synapses between the medial amygdala (MeA) and the ventromedial hypothalamus (VmH) and bed nucleus of the stria terminalis (BNST). Depotentiation of these pathways immediately after foot shock suppresses the increase in aggression, while having no effect on anxiety-like, depressive-like, or non-aggressive social behaviors. This study identifies the MeA-VmH and MeA-BNST circuits and synaptic potentiation as neural substrates for traumatic stress-induced prolonged aggression increase and potential therapeutic targets in treating the aggression symptom of psychiatric illnesses such as PTSD.