A team of UC Berkeley neuroscientists have used advanced microscopy techniques to capture images of the brains of mice as they learned to problem-solve, according to a study published in Nature Communications on Monday.

The team — led by Linda Wilbrecht, a campus associate professor of psychology — was the first to photograph the rewiring of the brain at the synaptic level while higher-order learning took place. It found the mice’s brains, particularly their orbitofrontal cortexes, had been resculpted during the course of their experiments.

This resculpting, which was manifested in both gained and lost synaptic connections, provides strong evidence for the benefits of an “active learning” approach to learning that is composed of critical thinking, direct participation and strategizing.

“What was really interesting was that these gains and losses were not just correlated with the number of successful trials … but with the combination of the strategy the mice used and the outcomes of that strategy,” Wilbrecht said. “This result suggests that active learning, as opposed to passive learning, is important for problem-solving.”

In the experiments, mice were presented with a foraging challenge during which they would have to locate hidden food. For example, the researchers would isolate a mouse in an arena with four differently scented bowls, which would be moved around so the mice would learn to identify the location of a Cheerio solely by the smell of the bowls.

The mice were ultimately able to determine the bowl containing the Cheerio after 30 to 40 trials, in a time span of about an hour. After undergoing this “training,” the mice would be temporarily anesthetized and placed under a laser scanning microscope in order to photograph changes in their synaptic connections.

Wilbrecht and her team, including Harvard postdoctoral researcher and lead author Carolyn Johnson, were interested in how orbitofrontal cortexes impact human beings’ ability to make decisions. In particular, the team wanted to capture the mice’s changing abilities to understand and follow “rules” during their foraging tasks.

“The way we define a rule is the link between cues, actions and outcomes,” Wilbrecht said. “Rules don’t exist in the world, they exist in the brain. So Carolyn Johnson might just be the first person to catch a glimpse of a rule.”

According to Michael DeWeese, a campus associate professor of biophysics, “many studies” of humans have suggested the advantages of active learning over passive learning in forming such links between actions and outcomes. He was uncertain, however, whether Wilbrecht’s study of mice would be directly applicable to people.

“Undoubtedly, some results in mouse orbitofrontal cortex will translate to humans, but others won’t,” DeWeese said in an email. “My guess is that similar neural mechanisms are at work in both mice and humans for tasks that both species can perform, but time will tell.”