Lab rats show learning pathways in research study

Learning a complex skillful movement like tying your shoes or playing an instrument takes practice. After repeating the same movements over and over, people often develop a stereotypical way of performing the task and may not even have to think about it. Although we perform such repetitive tasks every day, little is known about how the brain learns, repeats and perfects them.

Steffen Wolff, PhD

Now a researcher at University of Maryland School of Medicine (UMSOM) and his colleagues at Harvard University have shown in rats how multiple regions of the brain must work together to learn a skill and reproduce it perfectly, with each rat adding its own personal flair in the form of a “dance”.

Their study was published on February 25, 2022 in Scientists progress.

“As well as following our basic curiosity to understand how the brain works and how we learn movement, our work has many direct applications. Understanding the conditions under which healthy brains learn explains how people should train for highly qualified as certain sports,” said the UMSOM Assistant Professor of Pharmacology. Steffen Wolff, PhD. “Most importantly, one day, hopefully, the knowledge gathered through this basic research program will help people with brain injuries or diseases that affect movement.”

The research team trains rats to study how their brains learn and perform new skills. In these experiments, rats learn to press a lever in a specific way to drink water.

“During the learning process, they develop a little dance, and each rat comes up with their own choreography,” Wolff said. “After perfecting their technique, they continue doing what worked for them when learning: one animal scratches the wall, another stamps its foot, and another sticks its tongue out, all while simultaneously pressing the lever.”

These dances resemble the superstitious moves that baseball pitchers perform every time they are about to throw the ball, like tugging on the brim of their hat or scraping sand with their foot.

In an earlier study, the team showed that when researchers damaged the motor cortex – part of the outermost layer of the brain – rats couldn’t learn their little dances. Yet once they had learned their dance to perform the task, they could perform it just fine without that brain region. In another study, the researchers discovered another brain area essential for learning the task: the basal ganglia, a deep region of the brain. This region is also affected in Parkinson’s disease.

In their latest study, the researchers put the pieces of the puzzle together by asking whether the motor cortex teaches the basal ganglia to produce the new skill. They used viruses to cut the connection between the two areas of the brain. As the researchers expected, they found that without the motor cortex teaching the basal ganglia, the rats could no longer develop any of their dances.

The researchers then wanted to see if the basal ganglia were also working with other regions of the brain to perform the learned skill. They focused on another deep region of the brain, which also has close ties to the basal ganglia – the thalamus.

When the researchers now interrupted the connection between the thalamus and the basal ganglia with their viral tool, the rats still pressed the lever, but they completely lost their idiosyncratic learned “dances”. The rats went back to knocking repeatedly on the lever, as they all did when they first started learning the task. Wolff explained that these simple movements could be produced by other more fundamental parts of the brain, such as the brainstem.

“This work helps reveal the logic of how individual brain regions work together to control skill learning and performance, a first step in our quest to help treat patients with motor disorders like Parkinson’s and injury from trauma or stroke controlling parts of the brain,” said Dean E. Albert Reece, MD, PhD, MBAChief Medical Officer, University of Maryland, Baltimoreand Professor Emeritus John Z. and Akiko K. Bowers, UMSOM.

The study’s other authors are Raymond Ko, PhD, and Bence Ölveczky, PhD, of Harvard University.

This study was supported by the National Institute of Neurological Disorders and Stroke (R01-NS099323-01, R01-NS105349), a European Molecular Biology Organization Postdoctoral Fellowship (ALTF1561-2013), and a Postdoctoral Fellowship from the Human Frontier Science Program (LT 000514/ 2014).

Paul N. Strickland