DESCRIPTION (provided by applicant): Aggression is an innate social behavior across invertebrate and vertebrate species. For most individuals, aggression is essential to protect their resources and ensure reproductive success when interference arises. However, for some individuals, aggression appears to be a source of pleasure. Many examples show that certain individuals across a range of species, from fish to primates, will voluntarily seek out the opportunity to engage in aggressive actions. For humans, bullying, stalking, and sexual predation are among the many forms of aggression-seeking behaviors that negatively affect our society. Treatments that suppress aggression-seeking behaviors would be especially useful given that they could prevent potential aggressive actions without compromising general social, cognitive, and motor abilities. Unfortunately, little is known about what brain activity promotes the aggression-seeking behavior and consequently no treatment is currently available to specifically suppress aggressive motivation. In response to this knowledge gap, our studies seek to understand how the aggressive impulses emerge in the brain. In our previous studies, we identified the ventrolateral part of the ventromedial hypothalamus (VMHvl) as being indispensable for inter-male attack. Whereas activation of the VMHvl induces acute attack towards both male and female conspecifics, suppression of the VMHvl reduces natural inter-male attack. However, it remains unclear whether the VMHvl only controls the motor expression of attack or also determines sensory-independent aggression- seeking behaviors. To address this question, we designed a "self-initiated aggression" (SIA) task that allows us to temporarily separate the seeking phase and the action phase of aggression. During the task, the animal learns to voluntarily nose poke to gain access to a weaker intruder that they can attack. Using this task, we found that the VMHvl activity can substantially modulate the aggressive motivation in mice. In this study we will follow up on these initial findings and examine the natural VMHvl cell activity during the SIA task at both the single-cell and population levels. Through this study we hope to shed some new light onto the neural origin of aggressive motivation.

PUBLIC HEALTH RELEVANCE: Individuals across vertebrate species demonstrate self-initiated aggression-seeking behavior that is analogous to "premeditated" aggression in humans and understanding the neural basis of such behavior might help to avert its potentially devastating effects on society. We recently found that a hypothalamic subnucleus is essential to control aggression-seeking behavior in mice. To understand how the aggressive motivation emerges in the brain, we will combine electrophysiological and optical imaging tools to investigate the responses of cells in this region when aggressive male mice actively seek out the opportunity to attack.