Spotlight: The Watt Lab

Watt lab logo of a neuron

Principal Investigator: Dr. Alanna Watt

Location: McGill University, Montreal, Canada

Year Founded: 2011

What disease areas do you research?

What models and techniques do you use?

Research Focus

What is your research about?

We are interested in how the cerebellum influences motor coordination in both the healthy brain and in models of disease and aging. By identifying changes in the cerebellum underlying ataxias and aging, we hope to discover new treatments for patients.

Why do you do this research?

We want to understand how the cerebellum works and use this knowledge to understand the changes in the cerebellum that lead to ataxia. As a lab, we are particularly interested in studying rare disorders like SCA6 and ARSACS.

These disorders have limited treatment options. We hope that by understanding how the cerebellum works differently in these disorders, we will be able to identify new treatments to help ataxia patients.

We are also interested in identifying common changes between different types of ataxia, to find out whether treatments identified in one form of ataxia might also help other ataxia patients.

Six slippers with a variety of designs, includes brain cells and mice

Fun Lab Fact

We got together and made our own slippers to keep cozy in our office. If you look at the picture closely you might be able to spot some cells from the cerebellum on some of them!

Image courtesy of Anna Cook.

For More Information, check out the Watt Lab Website!


Written by The Watt Lab, Edited by Celeste Suart

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

Continue reading “Molecular Mechanism behind Purkinje Cell Toxicity in SCA1 Uncovered”

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.

Continue reading “Accidental discovery reveals possible link between cerebellar function and motivation”

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

Continue reading “Protein kinase C to the Rescue in Spinocerebellar Ataxias”