A new study, published in the journal Current Biology, has discovered how violent rage is controlled within the brains of male mice. The research, led by New York University’s Langone Medical Center, found that unprovoked, angry outbursts within male mice are directly connected to the circuitry between two specific brain structures. By stimulating this connection, aggression can essentially be deactivated.

The lateral septum (LS) is located within the midbrain of mice, a small, central part of the brainstem. It’s known to researchers to play a key role in regulating emotional processes and responses to stress. In addition to this, the LS sends and receives signals to and from a brain region broadly linked to inducing aggression, the hypothalamus.

Dayu Lin, the study’s senior investigator and an assistant professor at NYU Langone's Druckenmiller Neuroscience Institute, decided to investigate what role the LS played in regulating aggression. In order to artificially stimulate the LS of laboratory mice, a probe was surgically inserted into their brains, which used pulses of light to excite specific brain cells (neurons).

Disabling the LS appeared to trigger a cascade of activity along a neural pathway leading to a specific part of the hypothalamus – the ventrolateral part of the ventromedial hypothalamus, or VMHvl. This induced something called “septal rage,” wherein physical aggression towards other mice was seen to dramatically increase. When the LS was stimulated by the probe, the neural pathway between the LS and the VMHvl fired up again. This stifled the flare up within the mice’s VHMvls, calming them down.

^{A graphic showing that stimulating the LS-VHMvl connection suppresses attack-excited cells, but activates attack-inhibited cells, within the mice. Wong et al./Current Biology}

However, one set of cells in the VHMvL showed increased activity even as the rest in this region became inactive. The researchers think that these cells are “attack-inhibited” cells, those that likely help to regulate aggressive behavior – although at present, they cannot be certain that this is indeed what the cells do.

On the other hand, the cells being deactivated during LS stimulation are most certainly “attack-excited” cells, which induce aggressive behavior. In this way, the LS appears to be a “smart gatekeeper,” simultaneously capable of deactivating pro-aggression cells and activating aggression suppression cells.

The LS is also known to be able to inhibit sexual behavior in mice. Intriguingly, however, this study appears to show that a mouse’s sexual behavior isn’t affected by interrupting the neural pathway between the LS and VHMvl. This demonstrates that aggression and sexual behavior, two neurologically-hardwired traits, are able to be regulated separately.

It’s worth noting that although septal rage is not yet known to occur in humans, this research may help map the neural circuitry that controls aggressive behavior, which could eventually lead to surgical treatment for humans.

“There’s clear evidence to suggest that aggression is a regulated phenomenon,” Lin told IFLScience. “In my opinion, the majority of problems that are related to hyperaggression that we observe in humans are likely due to misregulation of this type of neural pathway.”