What might be called the make love, not war branch of behavioral neuroscience began to take shape in (where else?) California several years ago, when researchers in David J. Andersons laboratory at Caltech decided to tackle the biology of aggression. They initiated the line of research by orchestrating the murine version of Fight Night: they goaded male mice into tangling with rival males and then, with painstaking molecular detective work, zeroed in on a smattering of cells in the hypothalamus that became active when the mice started to fight.

The hypothalamus is a small structure deep in the brain that, among other functions, cordinates sensory inputsthe appearance of a rival, for examplewith instinctual behavioral responses. Back in the 1920s, Walter Hess of the University of Zurich (who would win a Nobel in 1949) had shown that if you stuck an electrode into the brain of a cat and electrically stimulated certain regions of the hypothalamus, you could turn a purring feline into a furry blur of aggression. Several interesting hypotheses tried to explain how and why that happened, but there was no way to test them. Like a lot of fundamental questions in brain science, the mystery of aggression didnt go away over the past centuryit just hit the usual empirical roadblocks. We had good questions but no technology to get at the answers.

By 2010, Andersons Caltech lab had begun to tease apart the underlying mechanisms and neural circuitry of aggression in their pugnacious mice. Armed with a series of new technologies that allowed them to focus on individual clumps of cells within brain regions, they stumbled onto a surprising anatomical discovery: the tiny part of the hypothalamus that seemed correlated with aggressive behavior was intertwined with the part associated with the impulse to mate. That small duchy of cellsthe technical name is the ventromedial hypothalamusturned out to be an assembly of roughly 5,000 neurons, all marbled together, some of them seemingly connected to copulating and others to fighting.

Theres no such thing as a generic neuron, says Anderson, who estimates that there may be up to 10,000 distinct classes of neurons in the brain. Even tiny regions of the brain contain a mixture, he says, and these neurons often influence behavior in different, opposing directions. In the case of the hypothalamus, some of the neurons seemed to become active during aggressive behavior, some of them during mating behavior, and a small subsetabout 20 percentduring both fighting and mating.

That was a provocative discovery, but it was also a relic of old-style neuroscience. Being active was not the same as causing the behavior; it was just a correlation. How did the scientists know for sure what was triggering the behavior? Could they provoke a mouse to pick a fight simply by tickling a few cells in the hypothalamus?

A decade ago, that would have been technologically impossible. But in the last 10 years, neuroscience has been transformed by a remarkable new technology called optogenetics, invented by scientists at Stanford University and first described in 2005. The Caltech researchers were able to insert a genetically modified light-sensitive gene into specific cells at particular locations in the brain of a living, breathing, feisty, and occasionally canoodling male mouse. Using a hair-thin fiber-optic thread inserted into that living brain, they could then turn the neurons in the hypothalamus on and off with a burst of light.

Optogenetics: Light Switches for Neurons

Anderson and his colleagues used optogenetics to produce a video dramatizing the love-hate tensions deep within rodents. It shows a male mouse doing what comes naturally, mating with a female, until the Caltech researchers switch on the light, at which instant the murine lothario flies into a rage. When the light is on, even a mild-mannered male mouse can be induced to attack whatever target happens to be nearbyhis reproductive partner, another male mouse, a castrated male (normally not perceived as a threat), or, most improbably, a rubber glove dropped into the cage.

Activating these neurons with optogenetic techniques is sufficient to activate aggressive behavior not only toward appropriate targets like another male mouse but also toward inappropriate targets, like females and even inanimate objects, Anderson says. Conversely, researchers can inhibit these neurons in the middle of a fight by turning the light off, he says: You can stop the fight dead in its tracks.

Moreover, the research suggests that lovemaking overrides war-making in the calculus of behavior: the closer a mouse was to consummation of the reproductive act, the more resistant (or oblivious) he became to the light pulses that normally triggered aggression. In a paper published in Biological Psychiatry, titled Optogenetics, Sex, and Violence in the Brain: Implications for Psychiatry, Anderson noted, Perhaps the imperative to make love, not war is hard-wired into our nervous system, to a greater extent than we have realized. We may be both lovers and fighters, with the slimmest of neurological distances separating the two impulses.

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