Traumatic and stressful experiences are among the major causes of psychiatric disorders such as post-traumatic symptom disorders (PTSD) and depression. However, our understanding of the molecular and neural bases of the stress state and the chronic manifestations of mental illness as well as effective treatments are largely lacking. Aggression is prevalent in the animal kingdom and is influenced by genes and environment as well as GxE interaction (reviewed in Kim, 2016). Here, we investigated if repeated fighting encounters would induce an internal state that could affect the expression of subsequent behavior. We trained wild-type males to become winners or losers, by repeatedly pairing them with hypo- or hyper-aggressive opponents, respectively. Kim et al. (2018) observed that chronic losers tend to lose subsequent fights, while chronic winners tend to win them. Moreover, the effect of chronic losing experience generalized to other behaviors, such as gap-crossing and courtship, and the depressive-like behaviors were transmitted to F1 male offspring. We found that two conserved neuropeptide Y (NPY)-like neuropeptide F (NPF) and dopamine (DA) systems play central roles in the development of depression-like brain state. Furthermore, olfactory conditioning experiments showed that winning is perceived as rewarding, while losing is perceived as aversive. We showed that the activities of the PPL1-γ1pedc dopaminergic neuron and the MBON-γ1pedc>α/β mushroom body output neuron were required for aversion to an olfactory cue associated with losing fights. Currently we are studying the mechanisms of transgenerational epigenetic inheritance of aversive paternal losing experience. Subsequently, we will identify major neural chemicals and gene activities that could be of general importance in stress responses and coping mechanisms among diverse animals. The knowledge gained from these studies could be potentially useful for the development of new concepts and more effective treatments of stressful experience-induced psychiatric disorders.
Kim, Y.-K. (2016). A Drosophila model for aggression. In Animal Models of Behavior Genetics (J. Gewirtz & Y.-K. Kim), Springer, New York, New York, pp. 35-60.
Kim, Y.-K. Saver, M., Simon, J., Kent, CF, Shao, L, et al. (2018). Repetitive aggressive encounters generate a long-lasting internal state in Drosophila melanogaster males. Proc Natl Acad Sci USA 115, 1099-1104.
Animal models , Cognition: Education, Intelligence, Memory, Attention
