Spotlight: The Kuo Lab

Principal Investigator: Dr. Sheng-Han Kuo

Location: Columbia University, New York, NY, United States

Year Founded:  2012

What disease areas do you research?

What models and techniques do you use?

Kuo Lab group photo.
This is a group picture of the Kuo Lab. From the left to right: Nadia Amokrane, Chi-Ying (Roy) Lin, Sara Radmard, Sheng-Han Kuo (PI), Chih-Chun (Charles) Lin, Odane Liu, Chun-Lun Ni , Meng-Ling Chen, Natasha Desai, David Ruff.

Research Focus

What is your research about?

We study how mishaps and damage in the cerebellum lead to the symptoms experienced by ataxia and tremor patients. By looking at human brains, as well as brains from mouse models, we study how different changes in brain structure can lead to symptoms. This includes how well different parts of the brain can communicate with each other.

Why do you do this research?

When you ask patients about the challenges living with ataxia or tremor, they will talk to you about their symptoms. Symptoms can make different activities of daily living very challenging! By connecting specific brain changes to specific symptoms, we want to develop treatment options that target specific diseases. By doing this, we hope to improve patient’s quality of life. 

Initiative for Columbia Ataxia and Tremor Logo. It is a circle containing a lion with its whiskers to look like a neuron

The Kuo lab is part of the Initiative for Columbia Ataxia and Tremor. It’s a new Initiative at Columbia University to bring a group of physicians, scientists, surgeons, and engineers to advance the knowledge of the cerebellum and to develop effective therapies for ataxia and tremor.

Are you recruiting human participants for research?

Yes, we are! We are looking for participants for clinical research and trials. You can learn more about the studies we are currently recruiting for at this link.

Fun Fact

In the Kuo Lab, we call ourselves “the Protector of the Cerebellum in New York City”.

For More Information, check out the Kuo Lab Website!

We are looking for new graduate students and postdoctoral researchers to join our team. If you are interested in our work, please reach out to us


Written by Dr. Sheng-Han Kuo, Edited by Celeste Suart

Snapshot: What is the Morris Water Maze Test?

Spinocerebellar ataxias (SCAs) are well known for worsening motor coordination symptoms caused by the degeneration of the cerebellum. Yet, increasing reports indicate that broader changes are occurring in the brains of some SCA patients. This includes changes in the hippocampus, a brain region critical for learning and memory. One way to test learning and memory in mice is the Morris Water Maze Test. Researchers use this test on SCA mouse models to investigate how and when learning and memory symptoms arise. More importantly, we can also use this test to evaluate the effect of potential treatments on learning and memory.

white mouse swimming with its head poking up above the water
Although mice can swim quite well, they don’t like swimming. The Morris Water Maze takes advantage of this to test the learning and memory of mice. Photo used under license by Aleksandar Risteski/Shutterstock.com.

The Morris Water Maze consists of a large circular pool of opaque water. A platform is placed in the pool just under the surface of the water so that the mouse won’t be able to see it. Though mice are good swimmers, they don’t particularly enjoy swimming. Mice will always attempt to find the platform as quickly as possible. Shapes on the walls around the pool help the mice orient themselves within the pool (first panel in the figure below).

The first time a mouse swims in the pool (second panel in the figure), the mouse tends to swim aimlessly around until they eventually find the hidden platform. Each subsequent time the mouse swims in the pool, the mouse will get better and better. Using the shapes on the wall to help identify where they are in the pool, the mouse will eventually learn and memorize the platform’s location.

First day, mouse does not know wehere the plaform is an swims a lot. Second day, the mouse still swims a while but remembers where the platform is. On the last day, the mouse knows where the platform is and goes right there.
The three steps in the Morris Water Maze. Image made by Larissa Nitschke use BioRender.

As that happens, they will be better and better at the task. Eventually, the mice will swim immediately to the platform when placed in the pool (third panel in the figure). Researchers can measure this improvement by measuring how much time it takes the mouse to reach the platform and the length of its path to the platform. Additionally, to assess the strength of the memory, researchers can take out the platform from the pool in what is called a “probe trial”. Mice that spend more time in the area where the platform used to be are considered to have built the strongest memories of that location.

As is the case for some SCA mouse models, mice with impaired learning and memory have more difficulty learning and remembering the correct location of the platform. As a result, they spend a longer time searching for and swim longer distances to the platform. Overall, they display a poorer improvement over time. By using the Morris Water Maze Test on SCA models that receive different treatments, scientists can then further test which therapy could improve their learning and memory symptoms. Therefore, the Morris Water Maze Test may help identify new therapeutic strategies to treat learning and memory problems in patients.

If you would like to learn more about the Morris Water Maze, take a look at these resources by the Scholarpedia and JOVE.

Snapshot written by Carrie Sheeler and edited by Dr. Larissa Nitschke.

Snapshot: What is the balance beam test?

When you think of a balance beam, you might think of gymnastics. For humans, a balance beam is a surface where we perform jumps, flips, and other athletic feats. Whether it’s a child taking their first class, or an Olympic athlete going for gold, the balance beam requires both balance and coordination. When a scientist puts a mouse through the balance beam test, they don’t ask them to do this kind of complicated routine, but they are testing those same abilities.

Little Black Mouse on a White Background
Little Black Mouse on a White Background. Photo used under license by Michiel de Wit/Shutterstock.com.

The equipment setup for the balance beam test is simple: two platforms with a beam running between them plus lots of padding underneath so the mouse doesn’t get hurt if it falls off. Over multiple days, the scientist will train the mouse to run across the beam from one platform to another. Once the mouse has been trained, it will go through multiple official test runs. In these tests, the scientist will measure the time it takes for the mouse to cross the beam. They will also count the number of times one of its paws slips off the beam during the crossing. You can see some videos of mice doing the test here.

Mice that have problems with balance and coordination usually take longer to cross the balance beam and have more paw slips during the crossing. The mice might take longer to cross because they are clinging to the beam to try to stay on. Their paws might slip more because they cannot coordinate their movements properly. The scientist can also compare the measurements from the first day of training with the measures taken during the official runs. This shows how well the mouse learned to stay on the beam. This is useful because learning how to do a task and performing the task are two different things. Some parts of the brain are more important for learning, while others are more important for doing the task. Thus, telling those two aspects apart can be useful.

Mouse cossing a balance beam connecting two platforms

A typical balance beam setup, with two platforms and a beam between them. Image by Amy Smith-Dijak.

The balance beam test has been used to understand balance and coordination in both healthy mice and mouse models of disease. In healthy mice, scientists studying the basic biology of balance and coordination use this assay to test if changing the way particular parts of the brain work changes the mouse’s performance. For diseases in which lack of balance and coordination are major features, such as spinocerebellar ataxias, this test is a simple way to check how fast the disease progresses in mouse models. The assay can further be used to test possible treatments for these diseases: better scores after the treatment indicate that the therapy helped the mice improve their balance and coordination.

To sum it up, the balance beam test is a simple and effective assay to measure a mouse’s balance and coordination. Its use helps scientists to understand the basic biology of balance and coordination, as well as uncover why they are impaired in some diseases. Using the balance beam test on mouse models of disease that underwent different treatments, scientists can further measure if the therapy would improve the mouse’s balance and coordination. Therefore, the balance beam test might even help to find new treatments for motor coordination diseases.

If you would like to learn more about the balance beam test, take a look at these resources by the Maze Engineers and Creative Biolabs.

Snapshot written by Dr. Amy Smith-Dijak and edited by Dr.Larissa Nitschke.

Spotlight: The Movement Analysis and Robotics Laboratory (MARlab)

MAR lab logo

Principal Investigator: Dr. Maurizio Petrarca

Location: Bambino Gesù Children Hospital, Rome, Italy

Year Founded: 2000

What models and techniques do you use?

  • Wearable Technologies
  • Movement analysis
  • Robotics
  • Clinical standardized assessment tools
Seven researchers stand infrom of a presentation screen
This is group picture taken during a conference. From left to right: Silvia Minosse, Alberto Romano, Martina Favetta, Maurizio Petrarca (PI), Gessica Vasco, Susanna Summa and Riccardo Carbonetti. Image courtesy of Susanna Summa.

Research Focus

What is your research about?

MARlab has a lot of experience in the rehabilitation of children with motor disorders including cerebellar diseases. We specialize in the use of motion analysis systems and robotics. Using advanced tools, we customize assessments and rehabilitative settings matching children needs in an ecological context.

We are involved in research to define specific digital biomarker and we are exploring different technological solutions, including wearable technology, to monitor the patient at home.

Rehabilitative competencies assure clinical opportunity in developing technological tools for training and assessment of the postural control, upper-limb coordination, gait, speech and cognition in pathological conditions.

Why do you do this research?

Ataxias are rare and chronic diseases usually without cure. The progression of the disease needs to be monitored periodically, so patients visit the hospital to control their condition by performing several clinical protocols. Developing more accurate and precise technology, to measure symptoms remotely, will help us better measure the impact of different treatments and rehabilitation in ecological contexts, decreasing the patient’s stress. This will help researchers and doctors knowing what works best for the patient. 

Bambino Gesù Children Hospital Logo

The Movement Analysis and Robotics Laboratory (MARlab) is located in the Bambino Gesù Children Hospital in Rome, Italy.

Fun Fact

We are a pediatric hospital very close to sea and our walls are painted with underwater landscapes.

A hospital walkway with the walls painted with sea creatures and submarines

For More Information, check out the Bambino Gesù Children Hospital website!


Written by Dr. Susanna Summa, Edited by Celeste Suart

BDNF can reverse ataxia in SCA1 mice, even after symptom onset

Written by Anna Cook Edited by Dr. David Bushart

Brain-derived neurotrophic factor can prevent ataxia in SCA1 mice. New research shows that the treatment works even if it’s started after mice develop signs of ataxia.

SCA1 is a neurodegenerative disease caused by a mutation in the Ataxin1 gene. People with SCA1 often develop symptoms around 30-40 years old, although this can vary. The most common symptoms include ataxia, or movement problems that make it difficult to move and walk. These symptoms get progressively worse, eventually leading to problems with swallowing or speaking. There is currently no cure for SCA1 so it is important that research is conducted into potential treatments.

The lab of Dr. Marija Cvetanovic at the University of Minnesota has been using a mouse model of SCA1 to try to identify new treatments. In the past, these researchers have shown that a molecule called brain-derived neurotrophic factor (BDNF) could delay the onset of ataxia in a mouse model of SCA1.

A laboratory mouse sitting on a researcher's hand.
Research using SCA1 mice shows that BDNF treatment can have an impact, even after ataxia symptoms begin showing. Photo used under license by unoL/Shutterstock.com.

BDNF is a molecule found in the brain that is very important for healthy brain development. It is needed to keep many processes in the brain working normally. The researchers showed that levels of BDNF were reduced in the brains of SCA1 mice. The researchers injected BDNF into the brains of these mice to try to make up for the lost BDNF. This treatment, before the mice had begun to develop symptoms of ataxia, prevented the onset of motor problems and Purkinje cell death. You can read more about those findings in this past SCASource article.

This previous work was very promising, but there was one problem. In this study, the treatment was only tested before the SCA1 mice developed signs of motor problems or changes in their brains. In the real world, if we want to help SCA1 patients, we need treatments that will work even once the disease has started to progress. It was therefore important for the researchers to find out whether this treatment would work later in disease progression. That is exactly what they did next: In December 2020, the Cvetanovic lab published the results from their study testing BDNF as a treatment after mice had started to develop signs of SCA1.

Continue reading “BDNF can reverse ataxia in SCA1 mice, even after symptom onset”