A brain implant turns “loser” mice into aggressive fighters

 arstechnica.com  7/17/2017 11:55:23 PM   Annalee Newitz
Enlarge / Could this be the first step toward the Mouse Guard from David Petersen's amazing comic book?

It sounds like something out of a science fiction movie about making supersoldiers. Scientists have turned shy, low-ranking mice into aggressive fighters who almost always win in dominance competitions. And they did it by stimulating a part of the mouse brain that controls "effortful" behavior.

Mice are social animals, and male mice establish a pecking order amongst themselves by displaying aggressive behavior. Though this aggression can take many forms, neuroscientist Zhou Tingting of the Chinese Academy of Sciences, Shanghai, joined with his colleagues to measure mouse dominance using what's called the "tube test." The tube test creates a scenario in which there's not enough room for the mice to pass each other in the tube. Mice have to shove one another aside to get out. The mouse who shoves the most other mice out of its way will "win" the dominance game.

Mice shove each other in the tube test. Note that the winner isn't stronger—he's just more aggressive and persistent with his shoves.

In a recent article for Science, Zhou and his colleagues write that "winner
mice initiated significantly more pushes, and with a longer duration per push, than loser mice." Winners weren't stronger than losers; they were simply more persistently aggressive. The researchers also found that the winner mice showed brain activity in a cluster of neurons called the dorsomedial prefrontal cortex (dmPFC), which is associated with "effortful behavior" and "social dominance." Mice whose dmPFC was quiet during tube tests always lost.

Zhou and his colleagues wondered whether they could create "winner" mice by stimulating the dmPFC. Using a brain stimulation technique called "optogenetics" that triggers neural activity with proteins and light, they stimulated the dmPFC region of a low-ranking mouse's brain. Then the low-ranking mouse took the tube test with a high-ranking mouse. Immediately, the loser mouse began to shove the winner mouse vigorously, winning almost every contest.

Mice do the tube test after being subjected to brain stimulation via optogenetics, a technique that uses blue light to activate neurons. This time, the lower-ranked mouse wins out over the higher-ranked one.

There are a lot of interesting implications here for further research. First of all, winning social dominance contests is clearly not just a matter of physical strength. Having an aggressive attitude is key to winning. And second, there is the question of whether this kind of technique would work on other animals and perhaps even humans. Mouse brains are similar to human brains in some ways, but our brains are far more complicated. That makes it unlikely that a shy person could be transformed into RoboCop with just one squirt of photons from a brain implant.

Perhaps more interesting is how researchers found they could permanently transform loser mice into winners, just by stimulating their brains six or more times in tube tests. "We observed that not all the mice returned to their original rank," Zhejiang University neuroscientist Hu Hailan told the Guardian. "Some mice [did], but some of them had this newly dominant position." Hu and the other researchers refer to this as the "winner effect," in which one triumph can lead to more victories, due to a change in outlook.

Put in more scientific terms, the winner effect is the result of "neuroplasticity," or the way neural connections in our brains are constantly changing. Each time the mouse wins due to brain stimulation, the underlying structure of its brain changes a little bit. Over time, the mouse has essentially been rewired to be more aggressive in dominance games. Light stimulation isn't the only way to do this; animals can rewire their brains through new experiences or learning. But brain stimulation works remarkably fast.

For now, this research could only lead to a more aggressive mouse army. But in the future, it could help people overcome social anxiety by giving them a little boost of assertiveness at just the right moment. Or it could create an army of hyper-aggressive supersoldiers. What could go wrong?

Science, 2017. DOI: 10.1126/science.aak9726  (About DOIs).

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