Scientists develop tool to control the behavior of mice

What if you could control someone else’s behavior (without having to resort to guilt trips)?

Scientists, never held back by the notion of being too creepy, are starting to make this possible. Scientists have successfully remote-controlled people, putting stick-on electrodes on their legs to determine their walking direction. Others took over a beetle’s flight after hooking the insect up to a teeny wireless computer.

And now, a group of researchers at the University of North Carolina, Chapel Hill have developed genetic material that they can inject into mice brains that will alter their behavior, making them fitness nuts (or couch potatoes) or getting them to binge on cheese. (Sorry, diet nuts, they didn’t test making the mice starve themselves.)

In a nutshell, scientists cooked up a neuron-inhibiting receptor, called KORD. It shuts down a neuron when in the presence of salvinorin B, a molecule which hangs out in the brain but otherwise does nothing. When you’re throwing new receptors into a brain, it can sometimes mess things up a bit, but the researchers determined that it wasn’t producing any side-effects they didn’t want, such as the inability to feel pain or pleasure or making the mice walk funny.

That said, they were using special transgenic mice, engineered to express receptors in specific parts of the brain, such as those responsible for locomotion and feeding. To get the receptor into the brain, they have to essentially weaponize it, putting it into a virus that will “infect” the brain. During one set of experiments, the researchers injected the virus into a brain region known to decrease locomotion. When they gave these mice salvinorin B, it activated the KORD in that part of the brain which silenced the couch potato neurons and the rodents walked around more than control mice. The more salvinorin they got, the more they walked around. KORD activity had silenced the neurons that told the mice to sit still. Likewise, when mice that express KORD in regions of the brain that keep eating in check were given salvinorin, they tended to eat more.

Then, the researchers wanted to see whether they could increase and decrease these behaviors in the same animal. So they engineered a different mouse line to express both KORD and another engineered excitatory receptor. As expected, salvinorin B upped their movement. When they gave them clozapine-N-oxide, which activates the excitatory receptor, they started walking around less.

The work, which is described in a new study published today in the journal Neuron, is the first published project to come out of President Barack Obama’s BRAIN Initiative.

The receptor-engineering technology is dubbed of all things, DREADD — short for Designer Receptors Exclusively Activated by Designer Drugs, possibly not the best marketing given public concern over bioengineering animals and humans. As the name implies, “drugs” that bind to these special proteins don’t attach other types of receptors in the brain, so scientists can localize their effects.

It’s not a new concept. DREADDs have been used before to study how liver and breast cancer cells work. Neuroscientists have used them to figure out how neurons behave, but this is the first time scientists have been able to use them as an up and down dial. Before, they could only turn neurons on or off. Being able to control nerve cell’s activity bidirectionally gives scientists more flexibility in the types of experiments they’re able to do in the same set of animals.

“With its new push-pull control, this tool sharpens the cutting edge of research aimed at improving our understanding of brain circuit disorders, such as schizophrenia and addictive behaviors,” said Francis S. Collins, the director of the National Institutes of Health, one of the BRAIN Initiative funding agencies, in a statement. That’s going to take a while, but he’s right in saying that the types of technologies these researchers are developing are meant to help scientists figure out how different circuits in the brain work and what happens when they don’t function properly.

Before we go into full on dread-mode, it’s important to remember that they’re also unlikely to be ported to people any time soon. It’s hard to develop these things even in a model organism. Plus, there’s already a lot of debate over using gene-editing techniques in people, so legislators and activists are likely to be on the look-out for human applications, especially since doing this sort of thing in the human brain raises a special set of ethical conundrums.

Daniela Hernandez is a senior writer at Fusion. She likes science, robots, pugs, and coffee.