Scientists find a previously unknown role for the cerebellum

March 21, 2017 by Nathan Collins, Stanford University
Stanford researchers have found a previously unknown, cognitive role for the cerebellum’s granule cells, which show up as green in this image. Credit: Mark Wagner

Pity the cerebellum, tucked in the back of the brain mostly just keeping our muscles running smoothly. Its larger neighbor, the cerebrum, gets all the attention. It's the seat of intelligence, the home of thinking and planning. It's what separates humans from our less quick-witted ancestors. The cerebellum – which literally means "little brain" – is thought to just sit there helping us balance and breathe, like some kind of wee heating and ventilation system.

But maybe not for long. In a series of experiments published March 20 in Nature, Stanford researchers show that within the cerebellum respond to and learn to anticipate rewards, a first step toward a much more exciting future for the cerebrum's largely overlooked little brother and one that could open up new avenues of research for neuroscientists interested in the roots of cognition.

The conventional thinking: not thinking

Scientists had assumed the cerebellum helped control muscles mostly because of what happened when it got injured. "If you have disruption of the cerebellum, the first thing you see is a motor coordination defect," said the paper's senior author, Liqun Luo, an investigator at the Howard Hughes Medical Institute, professor of biology and member of Stanford Bio-X and the Stanford Neurosciences Institute.

Admittedly, there had been some hints of a larger role for the cerebellum, but scientists had a hard time following up on those hints in part because the neurons that make up most of the cerebellum are difficult to study. Those neurons, known as granule cells, account for 80 percent of the neurons in the brain – all packed into the cerebellum – but only about 10 percent of its volume. At that density, conventional techniques for recording cell activity don't work well, and without an effective way of studying granule cells in , scientists were left with an incomplete picture of what the cerebellum was really doing.

A new technology, and a helpful accident waiting to happen

Enter Mark Wagner, a postdoctoral fellow in Luo's lab who led the research with Tony Kim, a graduate student in the lab of Mark Schnitzer, an investigator at the Howard Hughes Medical Institute and an associate professor of biology and of applied physics. Wagner had not set out to redeem the cerebellum. He simply wanted to study how the cerebellum controls muscles in mice using a new technique that would allow him to record granule cells in real time.

Wagner had earned his PhD working with Schnitzer, who develops pioneering methods for imaging neuronal activity in fruit flies, mice and other living animals. One method, called two-photon calcium imaging, had the resolution Wagner needed to study mouse granule cells in action.

In order to study motor control, the team had to get the mice to move. In this case, mice received sugar water about a second after pushing a little lever. While the mice pushed levers and received their rewards, Wagner recorded activity in each mouse's granule cells, expecting to find that that activity in those cells would be related to planning and executing arm movements.

And to some extent he was right – some granule cells did fire when the animals moved. But other granule cells fired when the mice were waiting for their sugary rewards. And when Wagner sneakily took away their rewards, still other granule cells fired.

"It was actually a side observation, that, wow, they actually respond to reward," Luo said.

Putting the brain back together

That discovery is something of a revelation. For 50 years, the assumption was that granule – and by extension the cerebellum – performed only the most basic functions. But because no one had the tools to look closely at in action, "we just didn't know," Wagner said.

Now that scientists have a better idea of what's happening, Wagner's hope is that it could lead to something much bigger. "Given what a large fraction of neurons reside in the cerebellum, there's been relatively little progress made in integrating the cerebellum into the bigger picture of how the brain is solving tasks, and a large part of that disconnect has been this assumption that the can only be involved in motor tasks," Wagner said.

"I hope that this allows us to unify it with studies of more popular brain regions like the cerebral cortex, and we can put them together," Wager said, to figure out what's really going on inside our heads.

Explore further: Studies show that the cerebellum is crucial to understanding vulnerability to drug addiction

More information: Mark J. Wagner et al. Cerebellar granule cells encode the expectation of reward, Nature (2017). DOI: 10.1038/nature21726

Related Stories

Studies show that the cerebellum is crucial to understanding vulnerability to drug addiction

February 23, 2017
An international research team led by the Universitat Jaume I (UJI) has shown that the cerebellum, contrary to previous thought, fulfills functions that go beyond the motor sphere and can be co-responsible for the brain alterations ...

Dysfunction in cerebellar Calcium channel causes motor disorders and epilepsy

March 21, 2013
A dysfunction of a certain Calcium channel, the so called P/Q-type channel, in neurons of the cerebellum is sufficient to cause different motor diseases as well as a special type of epilepsy. This is reported by the research ...

Scientists find new clues to brain's wiring

July 18, 2014
New research provides an intriguing glimpse into the processes that establish connections between nerve cells in the brain. These connections, or synapses, allow nerve cells to transmit and process information involved in ...

Unlocking the secrets of nerve regeneration

June 29, 2016
Scientists at Hokkaido University, Japan, found that a glutamate receptor GluD2 was responsible for the regeneration of synapses in the cerebellum.

Researchers finds mechanism affecting alcohol consumption

August 30, 2016
A Washington State University researcher has found a mechanism that strongly influences whether or not an animal is likely to drink a lot of alcohol.

Recommended for you

Finding unravels nature of cognitive inflexibility in fragile X syndrome

January 22, 2018
Mice with the genetic defect that causes fragile X syndrome (FXS) learn and remember normally, but show an inability to learn new information that contradicts what they initially learned, shows a new study by a team of neuroscientists. ...

Epilepsy linked to brain volume and thickness differences

January 22, 2018
Epilepsy is associated with thickness and volume differences in the grey matter of several brain regions, according to new research led by UCL and the Keck School of Medicine of USC.

Research reveals atomic-level changes in ALS-linked protein

January 18, 2018
For the first time, researchers have described atom-by-atom changes in a family of proteins linked to amyotrophic lateral sclerosis (ALS), a group of brain disorders known as frontotemporal dementia and degenerative diseases ...

Fragile X finding shows normal neurons that interact poorly

January 18, 2018
Neurons in mice afflicted with the genetic defect that causes Fragile X syndrome (FXS) appear similar to those in healthy mice, but these neurons fail to interact normally, resulting in the long-known cognitive impairments, ...

How your brain remembers what you had for dinner last night

January 17, 2018
Confirming earlier computational models, researchers at University of California San Diego and UC San Diego School of Medicine, with colleagues in Arizona and Louisiana, report that episodic memories are encoded in the hippocampus ...

Recording a thought's fleeting trip through the brain

January 17, 2018
University of California, Berkeley neuroscientists have tracked the progress of a thought through the brain, showing clearly how the prefrontal cortex at the front of the brain coordinates activity to help us act in response ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

thingumbobesquire
5 / 5 (1) Mar 21, 2017
There are more things in heaven and earth, Horatio, Than are dreamt of in your philosophy.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.