by Cheshta Bhatia
figures by Jasmin Joseph-Chazan

Ubiquitous actions that we perform in our daily lives, like tying our shoelaces or playing basketball, rely on our brain’s ability to learn and execute motor skills; this ability to knit movements into a series of actions enables us to walk, dance, or play the piano. However, have you ever wondered why we can improve at these tasks with practice? A pianist can play several never-before-seen sequences by following sheet music, but is more likely to make mistakes than if they had practiced the music piece before. For a more seamless performance (such as in a concert), pianists practice the same piano sequence repeatedly until its execution becomes fast, stereotyped, and effortless. This concept of motor learning is not only limited to playing piano, but is implemented in everyday actions like driving, tying shoelaces, and walking as well.

What is motor learning and how does it work? 

Motor learning occurs as a result of practicing motor skills and is associated with long-lasting changes in the brain driven by cells known as neurons. These neurons use connections between one another, known as synapses, to receive, transmit, and process information between different brain regions. Just like friends communicate via telephone, brain regions communicate with each other using connections between neurons (Figure 1). These neuronal connections allow us to perform a wide range of actions, one of which is to learn motor behaviors. 

Figure 1: Just as friends interact with each other, brain regions communicate between one another via neuronal connections, or “synapses.

One major way in which information flows between neurons is by the release of chemical signals called neurotransmitters from one neuron to another. The nervous system has developed so that not all neurons are able to perceive every type of neurotransmitter. If that were the case, there would be no specificity, and all neurons would receive information at the same time; imagine if when you tried to call your friend on the telephone, your phone called 20 friends at once instead! A lack of specificity in neurotransmitter detection would lead to a burst of abnormal electrical signals, ultimately leading to a seizure. 

How can scientists figure out which neuronal connections are important for learning motor behaviors?

A rat’s brain, which is substantially smaller than a human’s, has connections between 12 billion neurons– how can scientists possibly deduce which neurons are important for motor learning in the much larger brains of humans? Luckily, mice and rats have long served as preferred species for biomedical research because of their physiological and anatomical similarity to humans, allowing scientists to use rats and mice as simpler systems to study behavior and the brain. So, how do we use the rat model system to identify which connections between brain regions are important for motor learning? One way this can be done is by blocking connections between specific brain regions. For example, consider three brain regions: A, B, and C. Region A communicates to regions B and C by releasing neurotransmitters that B and C recognize. If we block connections to region B, but not C, we can figure out what function each region has, as in this study (Figure 2). 

Figure 2:  Neurons of brain region A release a neurotransmitter that can be recognized by receptors present on neurons of region B and C. However, for experimental purposes, a researcher might want to specifically target particular connections. For example, a scientist  can block connections from A to B, while not affecting connections from A to C).

So, how do we block information transmission between A and B while keeping the connection between A and C intact? One way of doing this is by injecting a neurotoxin that blocks region A from communicating with all other regions. However, while this will prevent signaling from region A to region B, it will also block region A from communicating with region C, preventing us from our main goal of figuring out the specific role of connections between A and B. One alternative to get around this dilemma is to direct the neurotoxin to block the signaling between only two brain regions. To do this, we can leverage the Cre-lox mechanism, a genetic tool that provides cell-type specificity and allows the neurotoxin to block connections between specific brain regions of interest. 

Ultimately, these techniques can help us identify the connections in the brain that allow us to learn and improve motor behaviors with practice. For example, scientists can train rats to learn motor behaviors, such as rotating a joystick. By combining this behavior learning with the neurotoxin approach discussed above, scientists can silence specific projections in the brains of rats and observe how well they are able to learn this skill in comparison to rats that weren’t treated with a neurotoxin. If learning this behavior is impacted by blocking specific neuronal connections, it suggests that these connections are important for motor learning.

Why is studying motor learning important?

Motor learning is omnipresent in everyday actions. Whether it’s a baby trying to transition from crawling to walking or an adult learning a new dance move, every behavior is guided by the coordinated activity of neurons. Therefore, to understand the mechanistic basis of motor behaviors, it’s essential to delve deeper into the brain and identify which neural connections  work to generate complex behaviors. This research may also help us understand many neurological disorders, like Parkinson’s Disease (PD), in which patients have impaired motor coordination. Determining which connections in the brain control motor learning could help identify the neural mechanisms that deteriorate during PD and bring us closer to better treatments for complex neurological diseases. 

Cheshta Bhatia is a first year PhD student in the Organismic and Evolutionary biology program at Harvard university. She studies the neural circuits guiding motor behavior. 

Jasmin Joseph-Chazan is a third year PhD student in the Immunology program at Harvard Medical School.

For More Information:

  • To read more about how scientists use neurotoxins to silence synapses and understand motor behaviors, see this recent article.
  • For  more information about how the Cre-Lox system helps achieve specificity in lab animals, read this overview article.
  • Learn more about Parkinson’s disease here.

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