Exercise boosts motor skill learning via changes in brain's transmitters

Researchers find switch in chemical messaging is key prelude to motor skill acquisition

May 4, 2020

Science Daily/University of California - San Diego

Comparing the brains of mice that exercised with those that did not, researchers found that specific neurotransmitters switched following sustained exercise, leading to improved learning for motor-skill acquisition. Underscoring the critical benefits of exercise, even in a time of a global pandemic, the researchers found that mice that exercised acquired several demanding motor skills such as staying on a rotating rod or crossing a balance beam more rapidly than a non-exercised group.

Doctors have relentlessly impressed upon us the many benefits of exercise. Energy, mood, sleep and motor skills all improve with a regular fitness regimen that includes activities such as running. This has become of particular interest in the time of the COVID-19 pandemic.

But what happens in the brain during these improved states of health? The underlying neurological changes that open the door to these benefits have been unclear.

Now, Assistant Project Scientist Hui-quan Li and Distinguished Professor Nick Spitzer of the University of California San Diego have identified key neurological modifications following sustained exercise. Comparing the brains of mice that exercised with those that did not, Li and Spitzer found that specific neurons switched their chemical signals, called neurotransmitters, following exercise, leading to improved learning for motor-skill acquisition.

"This study provides new insight into how we get good at things that require motor skills and provides information about how these skills are actually learned," said Spitzer, the Atkinson Family Chair in the Biological Sciences Section of Neurobiology and a director of the Kavli Institute for Brain and Mind.

The study's results are published May 4 in Nature Communications.

Spitzer's laboratory discovered neurotransmitter switching in the adult mammalian brain and has led groundbreaking research on the ability of neurons to change their transmitter identity in response to sustained stimuli, typically leading to changes in behavior. After carrying out research that described neurotransmitter switching in depression, Spitzer and his colleagues began to turn their attention to how such switching might be involved in healthy conditions.

Li says the results underscore the importance of exercise, even at home during the current pandemic quarantine situation.

"This study shows that it's good for the brain to add more plasticity," said Li. "For people who would like to enhance their motor skill learning, it may be useful to do some exercise to promote this form of plasticity to benefit the brain. For example, if you hope to learn and enjoy challenging sports such as surfing or rock climbing when we're no longer sheltering at home, it can be good to routinely run on a treadmill or maintain a yoga practice at home now."

During the new study, Li and Spitzer compared mice that completed a week's worth of exercise on running wheels with mice that had no access to running wheels. They found that the exercised group acquired several demanding motor skills such as staying on a rotating rod or crossing a balance beam more rapidly than the non-exercised group.

When the brains of the running mice were examined, a group of neurons in the brain region known as the caudal pedunculopontine nucleus (cPPN) that regulates motor coordination was discovered to have switched neurotransmitters from acetylcholine to GABA.

To confirm their findings, the researchers used molecular tools to block the newly identified transmitter switch resulting from exercise. They found that the enhancement of motor skill learning in these mice was prevented. Based on their findings, the researchers propose a new model in which conversion of cPPN excitatory cholinergic neurons to inhibitory GABAergic neurons provides feedback control regulating motor coordination and skill learning.

The researchers say the discovery could lead to further findings where neurotransmitter switching leads to key motor skill changes. The researchers say they'd like to test ideas such as whether neurotransmitters could be deliberately switched to benefit motor skills, even without exercise. They also plan to conduct research on whether exercise similarly triggers benefits of motor skill learning in those with neurological disorders.

"We suggest that neurotransmitter switching provides the basis by which sustained running benefits motor skill learning, presenting a target for clinical treatment of movement disorders," the authors conclude in the paper.

Says Spitzer: "With an understanding of this mechanism comes the opportunity to manipulate and to harness it for further beneficial purposes. In the injured or diseased individual, it could be a way of turning things around... to give the nervous system a further boost."

https://www.sciencedaily.com/releases/2020/05/200504074712.htm

Go for a run or eat chocolate: A choice dictated by the cannabinoid receptors

March 19, 2019

INSERM (Institut national de la santé et de la recherche médicale)

Physical inactivity is a common factor in lifestyle diseases -- and one that is often linked to the excessive consumption of fatty and/or sugary foods. The opposite scenario of excessive physical activity at the expense of caloric intake can also be harmful, as cases of anorexia nervosa illustrate. These data therefore point to the crucial need to research the neurobiological processes that control the respective motivations for exercise and food intake. A study by Inserm and CNRS researchers published on March 7, 2019 in JCI Insight reveals that the cannabinoid type 1 (CB1) receptors play an essential role in the choice between running and eating chocolatey food.

The authors of this paper had previously reported that the cannabinoid type-1 (CB1) receptors, present on several types of neurons, play a key role in performance during physical activity in mice. A conclusion based on the performances achieved by animals with free access to an exercise wheel -- a model in which it was not possible to distinguish the mechanism involved (motivation, pleasure...). Given that the motivation for a reward can only be estimated by measuring the efforts that the individual -- whether human or animal -- is prepared to make to get that reward, the researchers devised a model in which each access to the wheel was conditional on a prior effort. This involved the animal repeatedly introducing its snout into a recipient, an essential prerequisite for unlocking the wheel. After a training period during which the level of effort required to unlock the wheel remained the same, the mice were confronted with a test in which the effort required was gradually increased. When exposed to this test, the mice lacking CB1 receptors showed an 80 % deficit in the maximum effort they were prepared to make to unlock the wheel, and without a decrease in performance during their access to it. This finding indicates that the CB1 receptors play a major role in controlling motivation for exercise. The use of other genetically-modified mice also enabled the researchers to demonstrate that these CB1 receptors controlling motivation for exercise are located on GABAergic neurons.

The researchers then examined whether the CB1 receptors in the GABAergic neurons control the motivation for another reward: chocolatey food (like humans, mice love it even when they are otherwise well-fed). While the CB1 receptors also play a role in motivation for food -- albeit to a lesser extent than in motivation for exercise -- the CB1 receptors located on the GABAergic neurons are not implicated in the motivation for eating chocolatey food.

In our daily life, we are faced with an ongoing choice between various rewards. A fact which has encouraged the researchers to develop a model in which following a learning period the mice had the choice -- in return for the efforts described above -- between exercise and chocolatey food. The motivation for exercise was greater than that for chocolatey food, with the exception of the mice lacking CB1 -- whether generally or just on GABAergic neurons -- whose preference was for the food.

In addition to these findings indicating that the cannabinoid receptor is essential for the motivation for exercise, this study opens up avenues for researching the neurobiological mechanisms behind pathological increases in this motivation. One illustration is provided by anorexia nervosa which often combines the decreased motivation to eat with an increased motivation to exercise.

https://www.sciencedaily.com/releases/2019/03/190319121721.htm