Published online 9 February 2011 | Nature | doi:10.1038/news.2011.82

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Cells lurking deep in the mouse hypothalamus help determine whether it fights or mates.

Violent behaviour in mice has been tracked to neurons within a part of the brain associated with sex. Moviestore collection Ltd/Alamy

Sex and violence are intertwined in mice. A tiny patch of cells buried deep within a male's brain determines whether it fights or mates, and there is good reason to believe humans possess a similar circuit.

The study, published in Nature today1, shows that when these neurons are quieted, mice ignore intruding males they would otherwise attack. Yet when the cells are activated, mice assault inanimate objects, and even females they ought to court.

The cells lie within an area of the hypothalamus with known links to violent behaviour. An electrical jolt to this vicinity causes cats and rats to turn violent, but neurophysiological experiments conducted decades ago stimulated too big an area to identify the specific brain circuits, let alone the individual neurons, involved in aggression.

More recently, scientists studying mice engineered to lack specific genes have found that some of them act more aggressively than normal mice. "We really don't know which part of the brain went wrong in those mice. Consequently it's tough to make sense of that behaviour," says Dayu Lin, a neuroscientist now at New York University and an author of the study, who began searching for the seat of aggression in mice while working with David Anderson at the California Institute of Technology in Pasadena.

Snapping into action

Unlike with cats and rats, zapping a male mouse's hypothalamus with electricity fails to make it more bellicose. To understand which other areas might be implicated in violent behaviour, Lin and Anderson's team exposed male mice to consecutive encounters with other intruding male and female mice. They then examined the brain areas activated by the encounters by labelling brain cells with a fluorescent tag that can distinguish recently active neurons. Surprisingly, neurons within a region called the ventromedial hypothalamus (VMH) snapped into action during fights — but also during sex.

Perplexed, the team implanted male mice with electrodes capable of measuring single cells in this area of the brain and watched what happened when mice fought or mated. Most of the neurons fired specifically during sex or bouts of violence, but a handful fired during both of these seemingly opposing behaviours.

The researchers next infected neurons in this region with a virus that inserts a gene that renders them responsive to blue light — a technique called optogenetics. With an optic fibre implanted into the brains of these mice, Lin and Anderson could fire these neurons on command.

When they did so, male mice wasted little time attacking other intruding males. Activating neurons in the aggression centre also provoked assaults on castrated males, whom males would usually ignore, as well as anesthetized animals and even an inflated laboratory glove.

Switching on these neurons also drove males to attack females (see video) — but only up to a point. When males first encountered a female, activating the neurons sent them into attack mode. However, if sex had already ensued, the researchers could not elicit the mice to attack. "It's kind of in its own world. It doesn't listen to anything else," Lin says. However, activating the aggression circuit post-coitus provoked a swift attack on the female.

Quieting the aggression centre also stopped mice from acting on violent urges. Animals expressing a gene in these cells that silences them didn't attack intruding males, though their sexual appetites remained.

Entangled circuits

Lin and Anderson hypothesize that the entanglement of brain circuits involved in sex and violence could help mice to respond appropriately to intruders, whether male or female. The neurons activated by sex, they suggest, suppress the urge to lash out against an unknown female.

"There is a need to protect their own territories against a male invader and a need to have sex with female invaders, and this is sort of built into the circuitry of the brain," says Clifford Saper, a neuroscientist at Harvard Medical School in Boston, Massachusetts. "It's the way animals protect their territory so they have enough room to feed their progeny."

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The same circuits probably exist in humans, too, says Newton Canteras, a neuroscientist at the University of São Paulo in Brazil. Deep-brain electrical stimulation has linked the VMH to defensive behaviour such as panic attacks, and the region is likely to be involved in aggression as well, he says.

"I think there's every reason to think that this would be true in humans," says Anderson. The hypothalamus is one of the brain's oldest structures, and the region is also linked to aggression in monkeys.

Perhaps, Anderson says, the brain pathway his team identified could malfunction in some violent sex offenders. "Maybe in those individuals there's some sort of miswiring in these circuits in the brain, so the violent impulses and sexual impulses are not properly segregated from each other."