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See Inside July / August 2011

An On/Off Switch for Sex and Violence

Using optical and genetic techniques, neuroscientists have identified an "on/off" switch for aggression in the brain



Barnaby Hall Getty Images

RECENTLY DEVELOPED powerful, yet also delicate and refined, genetic tools can inva­sively probe nervous systems of animals, far surpassing the safer but much cruder techniques that psychologists and cognitive neuroscientists use to observe the human brain. Now in a remarkable series of experiments, researchers have located a trigger for aggression in mice—providing us with fresh insights into the workings of our human consciousness.

You might object that mice and men are not the same and that studying the murine mind is different from studying the human mind. This fact is obviously true. Yet both Mus musculus and Homo sapiens are nature’s children, sharing much perceptual, cognitive and affective processing. The same process of relentless evolutionary selection has shaped both species—our last common ancestor was a mere 75 million years ago. The structure of their brains, and of their genomes, reflects this similarity. Indeed, only a neuroanatomist can tell a rice grain–size piece of mouse cortex from the same chunk of human cortex. If you think of a mouse as a mere automaton, Google “world’s smartest mouse.” The top hit will be a YouTube video of Brain Storm, a cute brown mouse running a complicated obstacle course—crossing an abyss on a rope; jumping through hoops; going up and down a seesaw, over a pencil, up a steep incline and down a ladder; and navigating around obstacles. It hesitates on occasion, sniffs the air but, once started, speedily completes the circuit.

The amazing finesse and utility of contemporary molecular biology techniques are illustrated in recent experiments dealing with sex and power—the twin themes around which much of popular culture, psychoanalysis and art is centered.

Aggression Center
Our story starts in the hypothalamus, an ancient region of the brain, conserved throughout mammalian evolution. In humans, it is about the size of an almond, housing a motley collection of neurons. These cells regulate distinct bodily functions such as temperature, circadian rhythms, sleep, hunger, thirst, sex, anger, aggression and response to stress. Earlier work showed that electrical stimulation of some of these sites provokes cats and rats to sudden bouts of rage and that the ventromedial hypothalamus (VMH) has some involvement in sexual behaviors. Yet the precise location of attack-promoting neurons, their mode of action, and the interplay between aggression and mating—normally two opposing forms of social inter­actions—had remained deeply mysterious.

Enter a team from the California Institute of Technology, under the leadership of neurobiologist David J. Anderson. In four steps, the seven scientists, spearheaded by postdoctoral fellow Dayu Lin (now at New York University), nailed down the critical role of aggression neurons in the VMH. The setting was the home cage of an individually housed, sexually experienced male mouse. When another mouse, either a male or a sexually receptive female, entered the cage, the resident male mouse usually attacked the former but mated with the latter. The scientists video recorded the behavior so that the detailed time course of interaction of every pair of animals—the cautious sniffing and retreating, the pushing, shoving and biting, the mounting and consummatory activities—in hundreds of encounters could be statistically analyzed and time-aligned using software developed by machine vision engineers ­Piotr Dollar and Pietro Perona.

The first experiment is a molecular biology version of brain imaging. By detecting the presence of c-fos, a protein that is rapidly synthesized following neuronal activity, researchers can identify nerve cells that are involved in some behavior. Unlike functional MRI, which visualizes “voxels” of active gray matter containing upward of one million neurons, this method homes in on individual cells. A subset of neurons within the VMH, termed the ventrolateral region of the VMH (VMHvl), became active following male-male encounters that ended up in fights. Similar results occurred in males mating with females. But were these neurons the same or different cells? With help from collaborators at the Allen Institute for Brain Science in Seattle, the team applied a variant of the c-fos method that distinguishes the neurons activated in two different, successive behavioral encounters. These results indicated that, surprisingly, many brain regions surveyed contained separate but intermingled populations of neurons activated during fighting versus mating, with only a small degree (about 20 percent) of overlap.

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