Snapshot: What is the Cerebellum?

The cerebellum, often referred to as the “little brain”, is part of the brain that is located behind the cerebrum (forebrain). The cerebellum accounts for about 10% of the brain’s volume. Despite occupying a small volume, the cerebellum contains more than half of the neurons in the brain. Most of the evolutionary research with respect to the brain has been focused on the forebrain; however, recent evidence suggests that the expansion of the size of the cerebellum might have given humans an edge with respect to higher behavioral functions, such as the use of tools. Therefore, the cerebellum has played a vital role during evolution, and this suggests an indispensable function for the human cerebellum.

cartoon diagram of the human brain, with the cerebelum coloured in pink
Diagram of the human brain, with the cerebellum highlighted in pink. Picture courtesy of Wikimedia Commons.

What does the cerebellum do?

For several decades, scientists believed that the main role of the cerebellum was to maintain posture and balance, to fine-tune motor movements, and to enforce motor learning. If you think about performing a certain movement (these thoughts happen in the forebrain), the cerebellum compares these “movement plans” with what movements were actually made and corrects for errors if there were any. This fine-tuning makes movements precise and is critical for making voluntary movements such as walking, running, or speaking. Therefore, it is with the help of the cerebellum that we learn to get better at throwing a curveball, riding a bike, or learning any other complex motor tasks.

Is that all the cerebellum does?

Well, scientists used to think so. Over the past two decades, new evidence has made scientists to re-evaluate their thoughts about the cerebellum. Scientists now believe that the role of the cerebellum extends beyond fine-tuning motor movements, and likely includes cognitive functioning and certain reward-seeking behaviors. However, this aspect of cerebellar function is still being studied and there is a lot for scientists to uncover.

What happens when the cerebellum is damaged?

The cerebellum is one of the primary culprits in many types of cerebellar ataxia, where the damaged cerebellum forces the affected individuals to gradually lose their ability to walk. Therefore, it is imperative to better understand how the cerebellum contributes to ataxia to provide better treatment for patients. Apart from ataxia, the cerebellum may also contribute to other disorders such as dystonia, Parkinson’s disease, Huntington’s disease, Alzheimer’s disease, and autism spectrum disorders. Therefore, understanding what happens when the cerebellum goes awry is critical for improving the quality-of-life for patients all over the globe.

If you would like to learn more about the cerebellum, take a look at these resources by the Khan Academy and BrainFacts.org.

Snapshot written by Dr. Sriram Jayabal and edited by Dr. David Bushart.

Molecular Mechanism behind Purkinje Cell Toxicity in SCA1 Uncovered

Written by Dr. Chandrakanth Edamakanti   Edited by Dr. Hayley McLoughlin

Recent study decodes the protein signature of toxic Purkinje cells, finding that Purkinje cell mTORC1 signaling is impaired in SCA1.

Spinocerebellar ataxia type 1 (SCA1) is a late onset cerebellar neurodegenerative disorder caused by a mutation (in this case, an abnormal polyglutamine stretch) in the Ataxin-1 gene. People with this condition experience problems with coordination and balance, a set of symptoms known as ataxia. The protein produced by this faulty gene, ATXN1, is particularly toxic to the Purkinje cells, the sole output neurons of the cerebellum. However, the reason behind the selective toxicity of Purkinje cells in SCA1 is unknown.

The main focus of this article is to address this question. It is the first study to find the protein signature of toxic Purkinje cells in SCA1 mice. In the end, the authors identified widespread protein changes that are associated with Purkinje cell toxicity.

science laboratory
Image of scientific laboratory. Photo by Martin Lopez on Pexels.com

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Accidental discovery reveals possible link between cerebellar function and motivation

Written by Logan Morrison Edited by Dr. Sriram Jayabal

Stanford researchers accidentally discover a new role (reward prediction) for the cerebellum, the primary brain region affected by spinocerebellar ataxias.

Would you believe that the part of your brain that enables you to perform simple, everyday tasks (like jogging or walking) also controls your ability to do more complex tasks (like throwing a curve ball) with accuracy? It’s true! Every one of our body’s movements is adjusted by a brain region known as the cerebellum – a primary area of pathology in spinocerebellar ataxias. The name “cerebellum” is a combination of the Latin word for the brain – cerebrum – and the Latin suffix -ellus, which means small. While this “little brain” might not take up much room, it actually contains the vast majority of the nerve cells (known as neurons) in the central nervous system1. Take a look at the image included with this article to see for yourself: even without the red highlighting, the cerebellum should be instantly recognizable as the distinctive structure in the bottom right, so folded and densely-packed that it looks a bit like something you’d find on the branches of a fern or shrub. Among these many folds are the circuits that fine-tune our motor output, providing us with the ability to move our bodies with ease and precision.

Wagner et al image
MRI of human brain, with cerebellum circled in red. Image courtesy of the Central Nervous System – Visual Perspectives Project at Stanford University/Karolinska Institutet2

For decades, not much else was said about the function of the cerebellum beyond its primary role in tweaking movement. Recently, though, there have been some hints that there is more to this part of the brain than we might have thought: brain imaging studies of patients suffering from bipolar disorder, for instance, have sometimes shown abnormalities in the cerebellum3, 4. Cerebellar abnormalities have been implicated in a variety of other diseases, as well, including autism spectrum disorders, schizophrenia, Alzheimer’s disease, and multiple sclerosis5, 6. Now, thanks to the hard work of scientists at Stanford University7 – as well as a bit of luck – we know that the cerebellum is not only involved in how we move, but why.

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Protein kinase C to the Rescue in Spinocerebellar Ataxias

Written By Dr. Marija Cvetanovic   Edited by Dr. Sriram Jayabal

Protein kinase C: one protein that may help to protect against cerebellar neuronal dysfunction & death in spinocerebellar ataxias

Among the estimated 86 billion brain cells (known as “neurons”) in the human body (Azevedo et al., 2009), there is a small population of cells called Purkinje neurons. Though they only constitute a modest ~14-16 million cells, (Nairn et al., 1989), death or dysfunction in Purkinje neurons can cause you to lose your ability to walk coherently – a clinical symptom known as “ataxia.” This is because Purkinje neurons are the major work horse of the cerebellum, which is the part of the brain that fine-tunes our movement. While different types of hereditary spinocerebellar ataxias (SCAs) are caused by mutations in different genes, they all exhibit one thing in common: Purkinje neurons undergo severe degeneration. Neither the reasons for this selective vulnerability of Purkinje neurons in ataxia, nor how to increase their resistance to degeneration, are clear.

Three cartoon brains
Image courtesy of the The Internet Archive/Nielsen Malaysia

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Early Cerebellum Development Abnormality in Adult-Onset Spinocerebellar Ataxia Type 1

Written by Dr. Vitaliy V Bondar  Edited by Dr. Chandrakanth Edamakanti

Researchers for the first time identified that spinocerebellar ataxia type 1 (SCA1) may have roots in early cerebellar circuit malfunction.

Cartoon of a neuron
Artist representation of a neuron. Image courtesy of Pixabay

Since the discovery of the cause of SCA1, researchers have wondered: why does it take three to four decades of life for symptoms to reveal themselves? This late stage disease progression is surprising, given that early molecular changes are observed in many SCA1 animal models. Furthermore, this is true for many other neurodegenerative diseases (i.e., that molecular changes precede symptoms). Studying and understanding this delay in symptom onset may reveal potential treatment options to mitigate and slow down the progression of the disease.

The cerebellum is one of the most important brain regions for SCA1 research because it is responsible for the fine movement control that SCA1 patients have difficulty with. Moreover, the cerebellum is the brain region that degenerates the earliest in SCA1. Given that SCA1 symptoms strike late in adulthood, many scientists thought that there would not be any cellular changes during the cerebellum’s development (that is, early in SCA1 patients’ lives). However, Chandrakanth Edamakanti, a postdoctoral scientist in Puneet Opal’s laboratory at Northwestern University, has recently demonstrated that the stem cells in the cerebellum behave differently in SCA1. These stem cells, which exist in the cerebellum for the first three weeks after birth, help to complete cerebellar development by adding new neurons and supporting cells (known as glia). Dr. Edamakanti and colleagues have shown that, in SCA1, this process is disturbed, which likely contributes to Purkinje cell toxicity at later ages. This represents the first cellular and anatomical difference that has been seen in neurons prior to degeneration in SCA1. Other neurodegenerative diseases, including Alzheimer’s, Huntington’s and Parkinson’s, may also stem from such developmental defects that set the stage for later disease vulnerability.

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