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Scientists manipulated mice to make them lose track of time

Dopamine makes the time fly

SV Darmstadt 98 v FC Ingolstadt 04 - Bundesliga Photo by Simon Hofmann/Bongarts/Getty Images

The mystery of why “time flies when we’re having fun” is a little closer to being solved thanks to scientists who manipulated mice brains using light.

In a study published today in the journal Science, researchers at Portugal’s Champalimaud Centre for the Unknown stimulated certain brain cells (or neurons) in mice to make them produce more of a much-hyped chemical called dopamine. Dopamine can play a role in everything from attention to reward, and previous work suggests that it influences time perception, too, according to study co-author Bassam Atallah. When the scientists made mice produce more dopamine, the creatures underestimated time — meaning that it probably felt like time was going more quickly than it objectively was. Blocking the neurons from producing dopamine made them overestimate the amount of time that passed.

Though the study isn’t in humans, we do have very similar brain structures, says Atallah. The results tell us more about the biology behind measuring time and suggest that one day we could understand exactly what’s going on when it seems like the day is dragging or flying by.

Before they could control mice brains, researchers had to spend months teaching the animals how to estimate time. It worked like this: There was a contraption with three holes. The mouse stuck its nose in the hole in the middle, and a tone played. Some time would pass, and then another tone would play. If time that passed between the two tones was longer than 1.5 seconds, the mouse would get a reward only if it put its nose in the hole on the left. If the tone was shorter than 1.5 seconds, the mouse would get a reward only for putting its nose in the hole on the right.

By observing whether the mice knew which hole to go to, the researchers could figure out whether the animals could tell if more or less than 1.5 seconds had gone by. “The mice take two to three months to get very good, but the best ones are arguably as good as humans are,” says Atallah. “Though some mice are brighter than others.”

The next step was figuring out what’s happening in the brain as the mice make their decisions. To do this, the scientists inserted special proteins into the brains to make the dopamine-producing neurons light up whenever they’re active. This way, by measuring how much light gets released when the mice were being tested, they could see how much dopamine was involved in the process. The amount of dopamine increased when they heard both the tones.

But that could be a coincidence. It doesn’t necessarily prove that dopamine actually causes mice to figure out how much time passed. To do this, the researchers manipulated the neurons using a very precise technique called optogenetics. In optogenetics, you use light to turn on or turn off certain neurons. The researchers stimulated the neurons of four mice to make them produce more dopamine, and blocked the neurons of four mice to make them produce less. It turns out that dopamine does seem to slow down the internal clock. Plus, the overestimation or underestimation only happened when the neurons were being manipulated, so it wasn’t because the mice were learning to adjust.

It’s important not to generalize the results too much. Dopamine is produced in lots of places in the brain, but the research focused on one area called the substantia nigra pars compacta. They chose this area because people with Parkinson’s disease have trouble judging time, and that the disease destroys this region.

In addition, the team was measuring dopamine indirectly, says Patrick Simen, a neuroscientist at Oberlin College who was not involved in the study. Directly measuring dopamine is hard, and the scientists were instead measuring the general activity of the neurons that release dopamine. This is usually pretty accurate, but sometimes factors other than dopamine cause a cell to become activated. Still, “this is an example of the incredible power of optogenetics,” says Simen. A lot of previous work measured dopamine throughout the entire brain, which gives us less useful information. “The strongest point is that they then went on and specifically found those neurons,” he adds. “They said, ‘let’s not just do a correlational thing, let’s actually perturb those neurons.’ It’s remarkable.”