Source: Lifesciences database/Wikimedia Commons

Faster treadmill running speeds enhance associative learning in the cerebellum of mice, according to a new study by researchers at the Champalimaud Center for the Unknown. This paper, “Locomotor Activity Modulates Associative Learning in Mouse Cerebellum,” was published on April 16 in the journal Nature .

"The cerebellum is important for learning skilled movements. It calibrates movements in the face of a changing environment to coordinate them in a very precise way," lead author, Megan Carey, said in a statement. Carey is the principal investigator and group of the Neuroscience Program at the Champalimaud Center for the Unknown in Lisbon, Portugal.

The main takeaway from this study is that the faster mice ran on a treadmill, the faster and better their cerebellum learned an associative task called "delay eyeblink conditioning."

The authors describe the method of their latest research: “Here we investigated the effects of behavioral state, and specifically locomotor activity, on delay eyeblink conditioning, a cerebellum-dependent form of associative learning. In delay eyeblink conditioning, animals learn to close their eye in response to an initially neutral conditioned stimulus (CS) that is reliably predictive of an aversive unconditioned stimulus (US), such as a puff of air to the eye.”

To gain a better understanding of the cellular changes that accompany learning in the cerebellum, Carey and colleagues developed a conditioned learning task of teaching mice to blink their eyes in response to a flash of light that was coupled with a puff of air, while running at various speeds on a treadmill. Eyeblink conditioning is a common way to test the speed and efficacy of associative learning in the cerebellum.

The mice in this study who had their treadmills set at a faster speed learned to associate the flash of light (which normally doesn’t cause mice to blink) with a puff of air more quickly. So, even if there wasn’t a puff of air to accompany a flash of light, these mice automatically blinked. On the flip side, it took much longer for delay eyeblink conditioning to be encoded into the cerebellum of mice whose treadmills were set at slower speeds.

In a statement, first author of this study, Catarina Albergaria, summed up, “Our main finding was that we could make mice learn better by having them run faster.”

Notably, the researchers also found that subsequent eyeblink performance benefited from faster running speeds. "The mice performed less well when we slowed down the treadmill, and this happened at time scales of a few seconds,” Albergaria said.

After identifying a causal link between running speeds and associative learning in the cerebellum, the researchers were curious to pinpoint where this enhancement was taking place within the “little brain.”

For this phase of their study, the research team used optogenetics to stimulate specific neurons that project to the cerebellum called “mossy fibers.” Within the cerebellum, sensory information is relayed from mossy fibers to granule cells in a way that allows a single mossy fiber axon to influence a huge number of Purkinje cells.

Interestingly, when the researchers stimulated the mossy fibers using optogenetics, they observed enhanced learning on par with faster running speeds. Therefore, the researchers speculate that finding ways to directly stimulate mossy fiber activity might have the same benefits on associative learning as running. “It doesn't necessarily need to be locomotion; anything that drives an increase in mossy fiber activity could provide an equivalent modulation of learning," Albergaria said.

Despite these groundbreaking findings about associative learning in the cerebellum, the authors are quick to point out that faster running speeds may not necessarily enhance learning speeds in other brain regions. "We don't know whether this is true for other, non cerebellar, kinds of learning,” Albergaria cautions.

Do Faster Running Speeds Enhance Learning in the Human Cerebellum?

Source: Wikipedia/Public Domain

According to Albergaria, "The cerebellum is a well-conserved structure across species and there are circuits that are common across species." She speculates that future research based on these findings could help us better understand how locomotion influences associative learning in the human cerebellum.

"We tend to think that to manipulate the plasticity of the brain, so that people learn faster and slow learners improve, we have to use drugs. But here, all we had to do was control how fast mice were running to obtain an improvement. It would be interesting to see if this holds for humans, for cerebellar forms of learning — and even for other types of learning," Carey said in a statement.

The authors conclude, “Our results suggest that locomotor activity modulates delay eyeblink conditioning through increased activation of the mossy fiber pathway within the cerebellum. Taken together, these results provide evidence for a novel role for behavioral state modulation in associative learning and suggest a potential mechanism through which engaging in movement can improve an individual’s ability to learn.”

Future research in the Carey Lab will try to answer bigger questions, such as why walking and other types of aerobic exercise seem to help us coordinate thoughts, organize ideas, and come up with creative solutions. Anectodal evidence also links physical activity with "Aha!" moments. For example, Albert Einstein famously said of E = mc2, "I thought of that while riding my bicycle." Along this same line, Manish Saggar of Stanford University has found fMRI brain imaging evidence that enhanced cerebellum connectivity boosts creative capacity.

Megan Carey's cerebellar research in Lisbon dovetails beautifully with research on the cerebellum being conducted by Jeremy Schmahmann at Harvard Medical School in Boston. Schmahmann's "Dysmetria of Thought" hypothesis posits that the cerebellum helps us coordinate our thoughts in much the same way it helps us coordinate our movements.

For more see, "Jeremy Schmahmann Untangles the Perplexity of Our Cerebellum" and MINDlink Foundation: Connecting the Cerebellum to Cures.