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Posted: 2016-11-14T16:06:23Z | Updated: 2017-11-15T10:12:02Z

By Eric Boodman

At parties and bars, he introduces himself as a "rat tickler."

The title makes Shimpei Ishiyama sound like he belongs in some forgotten guild of yore, with the Victorian "pure-finders ," who collected dog dung for a living, and the "flankers and flaggers ," who kept partridges in the range of hunters' guns.

But he is, in actual fact, a neuroscientist, and his rat-tickling is anything but antiquated. By trying to titillate these rodents -- and recording how their neurons respond -- Ishiyama and his adviser are unraveling a mystery that has puzzled thinkers ever since Aristotle posited that humans, given their thin skin and unique ability to laugh, were the only ticklish animals.

Aristotle was wrong, it turns out. In a study published Thursday in Science, Ishiyama and his adviser, Michael Brecht, not only found that rats squeaked and jumped with pleasure when tickled on their backs and bellies, but also that these signs of joy changed according to the rodents' moods. And, for the first time, they pinpointed a cluster of neurons that makes this sensation so powerful that it causes an individual being tickled to lose control.

"It's truly innovative and groundbreaking," said Jeffrey Burgdorf, a neuroscientist at Northwestern University who reviewed the paper. "It takes the study of emotion to a new level."

Burgdorf has played a central role in our understanding of animal tickling. He was part of a team that first noticed, in the late 1990s, that rats make a symphony of noises when they are experiencing social pleasure. Others had already noted that they trill and yip and sing during sex and meals -- all above the range of human hearing -- but the lab where Burgdorf worked noticed that the rodents emitted similar sounds while playing. And so one day, the senior scientist in the lab said, "Let's go tickle some rats."

They quickly found that those cries of pleasure doubled. But other researchers didn't share the rats' joy. Prominent scientists of emotion tried to impede the publication, accusing the team of "the sin of anthropomorphism," Burgdorf and his colleague Jaak Panksepp wrote in a review paper in 2003.

Tickling -- and why it has such a powerful effect on us -- has remained largely mysterious.

"Here's the problem in a nutshell, and it's a little philosophical," Burgdorf told STAT. "In order for us to function, we have to ignore about 90 percent of our sensory information. We have to process only the important stimuli. What the brain is doing is saying this tickling is important, and I'm going to be able to discriminate this kind of stimulation from other kinds of stimulation."

Ishiyama, a postdoc at Humboldt University in Berlin, wanted to figure out how that worked.

Everyone knows how to titillate an ocelot -- you oscillate its tit a lot. But designing a rigorous experiment on how tickling is processed by rat brains isn't as obvious, and is hardly mainstream in neuroscience.

What Ishiyama did was to drill tiny holes into the rodents' skulls and insert wires into their brains that could pick up or elicit electrical currents. A day later, he said, they were fully recovered from the operation -- and were ready for tickling.

Using a terrarium typically reserved for lab shrews, Ishiyama made a "tickle box," covering its walls with black foam. Then, he lifted the rats out of their cages, bringing them to the box, and tickling them, on and off, for 15 minutes. All the while, their brain activity was being picked up by electrodes, zinging up through the holes in their skulls and along wires that fed into a computer, while a special microphone recorded their ultrasonic squeaks.

He found that certain networks of neurons in a brain region called the somatosensory cortex began to fire when he tickled the rats. It didn't start immediately; they had to learn first that Ishiyama's tickling hand wasn't a threat. Once they did, though, they went wild, chasing his hand when he stopped tickling them, making joy jumps and pleasure squeaks when he did.

"At the first day, they rarely chased my hand, they didn't recognize my hand as a playmate yet," he said. "But after a few days they learned, and they started playing with my hand."

What was surprising was that the same neurons in the somatosensory cortex fired while the rats were playing with his hand, as though the tickling was still going on.

"If I transfer them to the tickle box, some rats already start vocalizing because they know I will tickle them," said Ishiyama.

But when he put them in a stressful situation -- balancing them on a small platform with their nocturnal faces blinded by a bright light -- they no longer reacted to the tickling, either in their behavior or in their brain activity.

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To make sure that he had indeed found a place in the brain where tickling is processed, Ishiyama then stimulated that area with electrical currents. The rats began to jump like rabbits and sing like birds.

"The authors have been very adventurous; they are not looking under the streetlamp," said Daniel O'Connor, a neuroscientist at Johns Hopkins who studies touch, and who was not involved in the study.

O'Connor noted that the perception of touch -- the shape and texture of an object, whether it's vibrating -- are different from the emotions triggered, and neuroscientists often thought that the emotional response wasn't processed in the somatosensory cortex along with the more basic feelings. To him, that finding was very surprising.

"Why does the world literally feel different when you are stressed out?" he said. "This is a first step towards answering that question. It gives us a way to approach it with experimental rigor."