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Stanford University School of Medicine

Daedalus, or Icarus? A small set of nerve cells in the brain determines risk-preference settings

As Greek mythology has it, an ultra-smart tinkerer named Daedalus slapped together two sets of wings from wood and wax so he and his son, Icarus, could bust out of the labyrinth in which they'd been imprisoned. The wings worked, and off soared the duo into the blue sky and out past the shores of Crete.

But young Icarus, carried away by the freedom of flight, ignored Daedalus' warning not to fly too close to the sun. The wax melted, the wings wilted, Icarus sank into the sea and drowned.

As this story and many others illustrate, individuals vary in their appetite for risk. Inventors, investors, explorers and outré artists -- risk-takers one and all -- have made outsized contributions to civilization. But imprudent risk-taking can prove devastating, putting lives, jobs, finances and families at risk.

"Risky behavior has its moments where it's valuable. As a species, we wouldn't have come as far as we have without it," Stanford psychiatrist/neuroscientist/inventor Karl Deisseroth, MD, PhD, told me when I interviewed him for a news release I was writing about his group's new study in Nature. 

Most people -- adults, anyway -- run on the risk-averse side. Given a choice between, say, a guaranteed stable salary versus a roller-coaster income that's likely to wind up about the same or even a bit larger in the long run (think: running your own business), the average person typically picks the salary.

However, a minority tends to consistently prefer risk. Even nail-biter types sometimes shoot for the moon.

To explore these differences, Deisseroth and his colleagues (including Stanford psychologist Brian Knutson, PhD, who has spent a career exploring risk-taking among people) devised an experiment using rats. The team, spearheaded by graduate student Kelly Zalocusky, trained the rats to choose between a "salary" lever paying off a dependable amount of sugar water and a "freelance" lever spouting a variable volume that, over time, yielded the same amount. Two-thirds of the rats liked the salary. The rest of the rats consistently preferred to take their chances.

The researchers found that a disappointing outcome (not as much sugar water as expected) on the most recent go-round sets off a characteristic burst of signaling activity in a specific set of nerve cells in the rats' brains -- but mainly in the brains of risk-averse rats. In risk-seekers, this signal was much weaker, and these rats' risky behavior was more or less impervious to the audacity-damping effect of a recent disappointment.

The study proved that it was the firing of this "disappointment signal" that guides rats -- and, probably, humans -- to the straight and narrow path. High-roller rats, in which (the scientists showed) this signal ordinarily lacks effective strength, abandon their bet-the-ranch attitude if the signal is precisely reproduced via high-tech manipulation of the relevant brain circuitry.

Pramipexole, a drug prescribed for Parkinson's disease, has the unfortunate side effect of spurring some patients to gamble compulsively. Given to rats in the study, it erased risk-avoiders "disappointment signal" and turned them into risk-seekers.

Learning how to tweak this hard-lesson-learned circuitry just enough could someday help curb addictive and other risk-seeking behaviors -- or, alternatively, help overcome excessive timidity and escape the opportunity costs of a life only half lived. Even cautious Daedalus, after all, had the courage to spread his wings and take to the sky.

Previously: A word with Karl Deisseroth, Stanford bioengineer Karl Deisseroth wins 2016 Breakthrough Prize in life sciences, Hyperactivity in brain's "self-control" center may stifle the pleasure-seeking urge and Party animal: Scientists nail "social circuit" in rodent brain (and probably ours, too)

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