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Male mice engage in aggressive behavior towards other males. The ventrolateral subdivision of the ventromedial hypothalamus (VMHvl) is necessary and sufficient for generating attack behavior in male mice: lesion or pharmacogenetic silencing of this area prevents natural attack, whereas optogenetic stimulation of neurons in the VMHvl leads to excessive attack behavior, including attacks on female mice and inanimate objects. On page 596, Falkner et al. show that the VMHvl also regulates aggression-seeking behavior in which male mice work for the opportunity to access (and attack) weaker males.

The authors used a task in which male mice could nose-poke at one of two ports to gain access to a submissive male. Only about half of the mice tested executed the nose-pokes, and those that did were highly aggressive during their subsequent interactions with submissive males. In fact, these males showed signs of heightened aggression prior to training in the nose-poke task. In single-unit and optical recordings, the authors found that VMHvl neuron activity tracked aggression-seeking behavior in this task. Silencing VMHvl neurons with inhibitory DREADDs reduced attack behavior, whereas optogenetic stimulation of VMHvl neurons increased attack behavior.

Although the VMHvl has previously been linked to reactive aggression, this study shows that it is also involved in 'proactive' aggression seeking, in the absence of a social stimulus. This study could have implications for understanding unprovoked violence in other species, including individual differences in propensity for such behavior. The VMHvl has, however, also been implicated in regulating sexual behavior, so further work is needed to understand how this tiny subnucleus regulates a diverse portfolio of social behaviors.