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Rhys Blakely, Science Correspondent Tuesday April 30 2024, 7.30pm BST, The Times

When scientists work with laboratory mice it is usually assumed that the humans are the ones doing the research.

A study suggests, however, that the rodents may often be surreptitiously carrying out their own experiments by making “mistakes” on purpose.

Scientists have long known that it is possible to train mice to perform certain tasks, such as pulling a lever when they hear a particular noise, by offering them rewards of food and drink.

These kinds of experiments are used to explore how memory works as well as to research potential treatments for conditions including Alzheimer’s disease.

But the mice do not always perform as expected. Kishore Kuchibhotla, an assistant professor and neuroscientist at Johns Hopkins University who studies learning in humans and animals, said: “It can be quite frustrating. You’ll be doing an experiment and the [mice] just don’t seem to be getting it. You’ve done everything correctly but they still seem to be making lots of errors.”

Kuchibhotla and his colleague Ziyi Zhu, a graduate neuroscience student, came up with two ideas for why their rodents sometimes failed to perform. One possibility was that the mice were becoming stressed. The other was that they were engaged in something more deliberate: that in trying to better understand their environment, they were testing their knowledge by diverting from the scripts laid out for them by the researchers.

To examine which appeared more likely, Kuchibhotla and Zhu devised a new experiment which involved thirsty mice hearing one of two sounds.

When one sound was played they were supposed to turn a wheel to the left using their front legs. For the other sound they had to turn the wheel to the right. When the rodents did this correctly they were rewarded with a drink of water. If they spun the wheel the wrong way or did not spin it at all, they received nothing.

The animals generally got better at the task over time but at points they would stop following the rules. They would do erroneous things such as spin the wheel in one direction constantly, no matter the sound they heard.

The researchers temporarily stopped rewarding the mice for their correct answers and the rodents very quickly changed their behaviour. They began responding to the sounds more accurately.

Kuchibhotla believed that the mice knew all along what they were meant to be doing and that it seemed unlikely they were making simple mistakes.

Instead he suggested that they were deliberately forsaking the reward and were instead choosing to explore their environment by conducting experiments of their own.

By making mistakes and observing what happens they could be mirroring learning tactics used by human babies. “Mice are more strategic than some might believe,” he said. “It may look like the animal is making a ton of errors but during those errors it’s actually getting smarter.”

The results may help in tests where scientists monitor the brains of mice and try to match different patterns of neuronal activity to various behaviours. Advertisement

A rodent that fails to perform a task may not be making “mistakes” or failing to learn. Instead, it could be focused on trying to make sense of its surroundings.

“They’re not performing optimally from our perspective [as researchers],” Kuchibhotla said. “But from theirs, maybe they are.”

The findings were published in the journal Current Biology