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The Circuitry of Sex and Aggression

Originally published in NYU Neuroscience Journal Club

by Koichi Hashikawa, PhD

Aggression is essential for competing over limited resources and is observed in a wide range of animals. It is typically observed more frequently in males than in females, with some differences in aggressive behaviors between sexes, such as intensity, frequency, and pattern of motor actions. Given that aggression is more prevalent in males, our understanding of the neural basis for aggression has been more advanced in males by previous studies with relatively much less knowledge on female aggression.

Although the hypothalamus has been implicated in controlling aggression since the initial work of Walter Hess, a Nobel Prize winner, who evoked aggression by hypothalamic electric stimulation in 1930s, it took almost a century before Lin and Anderson identified a specific nucleus, ventromedial hypothalamus, ventrolateral part (VMHvl) as the aggression locus in 2011. They utilized optogenetic and pharmacogenetics to show that this small nucleus, consisting only ~10000 neurons in the mouse brain, is necessary and sufficient for male aggression. Moreover, the authors characterized natural neural activity in freely behaving animals and found a subset of cells encoding various phases of aggression (Lin et al., 2011). Follow-up studies have further identified a subpopulation of neurons in the VMHvl expressing Esr1/PR as male aggression substrate (Yang et al., 2013; Lee et al., 2014). In contrast, the same functional manipulation experiments in those studies did not observe significant behavioral effects on female aggression, concluding that VMHvl’s role in aggression is sexually dimorphic, crucial for males, but not for females. However, given that females’ aggression level is generally lower and more unstable than males’ aggression in previous studies, there remained a possibility that VMHvl’s engagement in female aggression was overlooked..


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