English Archives |

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. 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)

Principal Investigator: Dr. Maurizio Petrarca

Location: Bambino Gesù Children Hospital, Rome, Italy

Year Founded: 2000

What disease areas do you research?

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.

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.

Four diseases, One Gene: CACNA1A

Written by Dr. Judit Pérez Edited by Dr. David Bushart

A new case report describes how a new mutation in the CACNA1A gene causes ataxia with seizures.

Genes and their diseases

Hereditary ataxias are caused by mutations in different genes that affect how different parts of the brain and spinal cord work. Usually, the affected genes predict how one would expect the patient’s clinical signs and symptoms to look. The reverse can also be true. For example, a set of clinical signs and symptoms may raise suspicion of a known genetic disease, which allows doctors to perform focused genetic testing to confirm the diagnosis. These correlations are helpful for doctors and patients in understanding the diagnostic process and disease outlook.

New mutation, new disease

A study by Stendel and colleagues was inspired by a patient who developed ataxia in mid-adulthood that slowly worsened over the next decades of his life. The progression resembled that of spinocerebellar ataxias with repeat expansions in their genes as the culprits. However, when doctors performed the usual genetic testing for ataxia genes, they did not find a match. Nevertheless, suspicion for an ataxia gene playing a role remained high. The patient had experienced seizures as a child (called “absence seizures”), which didn’t entirely fit the picture of known SCAs. Where to go from here? The scientists next broadened their search to include 118 genes that are known to cause ataxia or other diseases that include ataxia symptoms. To their surprise, they found a previously unidentified mutation in a well-known ataxia gene called CACNA1A.

Human brain digital illustration. Electrical activity, flashes and lightning on a blue background. — CACNA1A is a gene that instructs brain cells to make a protein called Cav2.1, which helps neurons communicate. But now mutations in the *CACNA1A* gene are now connected to four different diseases. *Photo used under license by Yurchanka Siarhei/*Shutterstock.com.

Snapshot: What is the Hippocampus?

How do you remember your name? Thank your hippocampus, a part of the brain that lies buried in the cerebrum and plays an important role in memory. The hippocampus looks like a seahorse when removed from the brain and hence the name (derived from Hippokampus, the Greek word for seahorse). Our brain consists of two hippocampi, one in each brain hemisphere.

One of the most striking feature of the hippocampus was observed by the Nobel laureate, Santiago Ramón y Cajal, in the 19^th century. Cajal recorded his microscopic observation of the hippocampus in the form of beautiful hand drawings:

A very detailed sketch of the hippocampus on paper. The drawing looks very old. — The hippocampus, ink on paper – original drawing by Cajal. See more of Cajal’s drawings in this blog post by Margaret Peot.

He documented that neurons were arranged in unique layers in the hippocampus, a ground-breaking observation that proved to be useful several years later in studying how these neurons communicate with each other and form a circuit (think of it like a logic gate) for collecting and storing memories.

What is the function of the hippocampus?

In the 1950s, a patient named Henry G. Molaison, referred to as patient H.M., suffered from a severe form of epilepsy and went through a surgical procedure where a portion of his brain was removed in an effort to treat epilepsy. His surgery was of moderate success. He managed mild epilepsy for the next 58 years, however, he tragically lost the ability to form new memories as most of his hippocampi were removed during surgery.

H.M. served as the longest case study in history to understand the formation of memory in humans. The hippocampus is important for formation of new memories that we experience, known as explicit memory. This mostly involves remembering facts or events and over a period of time they get stored away permanently as long-term memory by a process called memory consolidation.

From H.M.’s case study it was clear that he was unable to form new memories as he lost the ability to consolidate them for future use. However, some of his long-term memory before the surgery such as events from his childhood or facts about his parents remained intact. This was fascinating for scientists as they were able to conclude that the hippocampus is necessary for memory consolidation but not for memory retrieval – a process required for recollecting memories from the place it was stashed away (this storage space could be in other brain regions), as in the case of H.M.’s older memories before his surgery.

The hippocampus also acts like a GPS in our brain and is important for another type of memory called spatial memory. Groups of cells in the hippocampus called “place cells” co-ordinate with another group of cells called the “grid cells” that exist in another brain region, and help us remember directions and navigate the space around us. The scientists who discovered these cells, John O’Keefe, May Britt-Moser and Edvard Moser were awarded the 2014 Nobel Prize in Physiology and Medicine.

How is the hippocampus affected in neurological disorders?

Many neurological disorders have ties to dysfunction/degeneration of the hippocampus. Most notably is Alzheimer’s disease (AD), with one of the earliest AD disease symptoms being the loss of spatial memory and short-term memory. A previous article summary in our website also explores how an ataxia related gene increases the risk for Alzheimer’s disease.

If you would like to know more about the story of H.M. and how he transformed our understanding of memory, you can learn more by reading “Permanent Present Tense” by Suzanne Corkin.

If you would like to learn more about the hippocampus, take a look at these resources by Medical News Today and Verywell Mind.

Snapshot written by Dr. Chandana Kondapalli and edited by Dr. Hayley McLoughlin.