Study sheds light on brain activity during learning in mice

By revealing for the first time what happens in the brain when an animal makes a mistake, Johns Hopkins University researchers are shedding light on the holy grail of neuroscience: the mechanics of how we learn.

The team pinpointed the exact moment mice learned a new skill by observing the activity of individual neurons, confirming earlier work that suggested animals are fast learners that purposely test the boundaries of new knowledge.

The federally funded work, which upends assumptions about the speed of learning and the role of the sensory cortex, and which the researchers believe will hold true across animal species including humans, is newly published in Nature.

"Looking at a tiny part of the brain in a mouse, we can understand how the brain learns, and we can makes predictions about how the human brain might work," said Kishore Kuchibhotla, a Johns Hopkins neuroscientist who studies learning in humans and animals. "The field of neuroscience has made great progress decoding motor activity and how the brain processes sight and sound. But a holy grail of this type of research is thought-what comes between the hearing and the doing-we're all still trying to understand the patterns of brain activity that underly higher-order cognitive processes. These findings are a step in that direction."

Although the ability to learn quickly would benefit any animal in the wild, animals studied in labs seem to learn slowly and methodically. It typically takes mice, for instance, thousands of tries to learn a task, several hundred at best.

Kuchibhotla's lab previously found that animals' performance doesn't necessarily sync with their knowledge-or that animals might know a lot more than they demonstrate in tests. The lab also found that animals that seem to be slow learners might be testing their new knowledge. But by merely watching animals struggle at tasks, they couldn't tell a slow learner from a strategic tester of boundaries.

We are interested in the idea that humans and other animals may know things about the world, things that they choose not to show. Our core question is what is the neural basis of this distinction between learning and performance."

Kishore Kuchibhotla, Johns Hopkins neuroscientist 

The researchers taught mice to lick when they heard one tone but not to lick when they heard a different sound. From the moment training began, the team recorded the activity of neurons in the auditory cortex, an area of the brain associated with hearing and perception.

There were two major surprises. First, the mice learned in 20 to 40 tries, "extraordinarily fast," according to Kuchibhotla. And second, this learning activity happened in the sensory cortex, something that has typically been associated with nonsensory brain areas.

"This work illustrates the importance of assessing how brain activity impacts behavior at different stages of the learning process and in different conditions," said first author Celine Drieu, a postdoctoral fellow studying neuroscience at Johns Hopkins. "Our results show that a sensory cortex does more than processing sensory inputs; it is also crucial to form associations between sensory cues and reinforced actions."

When the mice continued to make errors, licking at the wrong times long after their neural activity showed they'd learned the task, their brain activity confirmed to the researchers that the mice knew the rules of the game-they were just experimenting.

'We were able to decode the cognitive driver of an error," Kuchibhotla said. "We could tell if the animal was making a mistake or just wanted to give the other option a shot."

Once the mice had mastered the task and ceased their exploratory behavior, this higher-order activity started to diminish, and the sensory cortex was no longer involved in the task.

"We think this means that animals are smarter than we think, and that there are distinct brain dynamics related to learning. You might know something, but there's a parallel process related to how you use it. The brain seems wired to do that well, to allow us to toggle between performance and learning as we get better and better at something."