The Neural Mechanisms of Winner and Loser Effect

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ABSTRACT Aggression is an important social behavior widely observed across species, including humans. It is considered an innate behavior because its expression requires no learning. With the right sensory trigger, often one associated with conspecific competitors, aggression is expressed as a series of stereotyped motor actions. However, the readiness to express aggression, or aggressiveness, varies widely among individuals. Experiences of winning and losing are known to contribute to this individual variability. Winning leads to an increase in aggressiveness while losing decreases aggressiveness, a phenomenon termed the winner and loser effect. While key hormonal events accompanying winning and losing have been identified, the neural mechanisms underlying the winner and loser effect remain poorly understood. We hypothesize that the aggressiveness of an individual is determined by the efficiency of sensory-motor transformation of the aggression circuit, which is determined by the biophysical properties and synaptic transmission of cells in the circuit. Winning and losing experiences alter the excitability and/or communication of aggression-related cells and ultimately changes the readiness to attack. Leveraging upon our deep understanding of the aggression circuit in male mice, in this study we will test this hypothesis through three specific aims. First, we will simultaneously record the aggression-cue evoked in vivo neural responses and glutamatergic release from 13 brain regions along the sensory-motor pathway that mediates aggression and examine the response changes over repeated winning and losing experiences. Second, we will use in vitro patch clamp recording to investigate the intrinsic properties and synaptic transmission of aggression-related cells from animals with repeated winning, losing and social interaction experiences. Our preliminary results revealed that the aggression circuit undergoes two-stage plasticity, first synaptic plasticity and then cellular plasticity, over repeated winning. Following up on this initial finding, in Aim 3, we will address the contribution of synaptic plasticity to short- and long-term winner and loser effect and the induction of cellular plasticity. The significance of our study is that it addresses a fundamental neuroscience question -- how social experience alters the brain to influence innate behaviors. It will also provide new understanding regarding the neural mechanisms underlying individual variability in aggressiveness. Such understanding could ultimately lead to novel strategies for treating psychiatric patients suffering from exaggerated aggression.