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
A gut feeling for mental health
February 4, 2019
Science Daily/VIB (the Flanders Institute for Biotechnology)
The first population-level study on the link between gut bacteria and mental health identifies specific gut bacteria linked to depression and provides evidence that a wide range of gut bacteria can produce neuroactive compounds.
In their manuscript entitled 'The neuroactive potential of the human gut microbiota in quality of life and depression' Jeroen Raes and his team studied the relation between gut bacteria and quality of life and depression. The authors combined faecal microbiome data with general practitioner diagnoses of depression from 1,054 individuals enrolled in the Flemish Gut Flora Project. They identified specific groups of microorganisms that positively or negatively correlated with mental health. The authors found that two bacterial genera, Coprococcus and Dialister, were consistently depleted in individuals with depression, regardless of antidepressant treatment. The results were validated in an independent cohort of 1,063 individuals from the Dutch LifeLinesDEEP cohort and in a cohort of clinically depressed patients at the University Hospitals Leuven, Belgium.
Prof Jeroen Raes (VIB-KU Leuven): 'The relationship between gut microbial metabolism and mental health is a controversial topic in microbiome research. The notion that microbial metabolites can interact with our brain -- and thus behaviour and feelings -- is intriguing, but gut microbiome-brain communication has mostly been explored in animal models, with human research lagging behind. In our population-level study we identified several groups of bacteria that co-varied with human depression and quality of life across populations.'
Previously, Prof Raes and his team identified a microbial community constellation or enterotype characterized by low microbial count and biodiversity that was observed to be more prevalent among Crohn's disease patients. In their current study, they surprisingly found a similar community type to be linked to depression and reduced quality of life.
Prof Jeroen Raes (VIB-KU Leuven): 'This finding adds more evidence pointing to the potentially dysbiotic nature of the Bacteroides2 enterotype we identified earlier. Apparently, microbial communities that can be linked to intestinal inflammation and reduced wellbeing share a set of common features.'
The authors also created a computational technique allowing the identification of gut bacteria that could potentially interact with the human nervous system. They studied genomes of more than 500 bacteria isolated from the human gastrointestinal tract in their ability to produce a set of neuroactive compounds, assembling the first catalogue of neuroactivity of gut species. Some bacteria were found to carry a broad range of these functions.
Mireia Valles-Colomer (VIB-KU Leuven): 'Many neuroactive compounds are produced in the human gut. We wanted to see which gut microbes could participate in producing, degrading, or modifying these molecules. Our toolbox not only allows to identify the different bacteria that could play a role in mental health conditions, but also the mechanisms potentially involved in this interaction with the host. For example, we found that the ability of microorganisms to produce DOPAC, a metabolite of the human neurotransmitter dopamine, was associated with better mental quality of life.'
These findings resulted from bioinformatics analyses and will need to be confirmed experimentally, however, they will help direct and accelerate future human microbiome-brain research.
Jeroen Raes and his team are now preparing another sampling round of the Flemish Gut Flora Project that is going to start next spring, five years after the first sampling effort.
https://www.sciencedaily.com/releases/2019/02/190204114617.htm
Gut hormone increases response to food
Ghrelin promotes conditioning to food-related odours
December 12, 2018
Science Daily/McGill University
The holiday season is a hard one for anyone watching their weight. The sights and smells of food are hard to resist. One factor in this hunger response is a hormone found in the stomach that makes us more vulnerable to tasty food smells, encouraging overeating and obesity.
New research on the hormone ghrelin was published on today in Cell Reports on Dec. 4, 2018, led by Dr. Alain Dagher's lab at the Montreal Neurological Institute and Hospital of McGill University.
Previous research by Dr. Dagher's group and others demonstrated that ghrelin encourages eating and the production of dopamine, a neurotransmitter that is important for reward response. In the current study, researchers injected 38 subjects with ghrelin, and exposed them to a variety of odours, both food and non-food based, while showing them neutral images of random objects, so that over time subjects associated the images with the odours.
Using functional magnetic resonance imaging (fMRI), the researchers recorded activity in brain regions known to be involved in reward response from dopamine. They found that activity in these regions was higher in subjects injected with ghrelin, but only when responding to the images associated with food smells. This means that ghrelin is controlling the extent to which the brain associates reward with food odours.
Subjects also rated the pleasantness of the images associated with food odour, and the results showed that ghrelin both reduced the response time and increased the perceived pleasantness of food-associated images, but had no effect on their reaction to images associated with non-food odours.
People struggling with obesity often have abnormal reactivity to the food-related cues that are abundant in our environment, for example fast food advertising. This study shows that ghrelin may be a major factor in their heightened response to food cues. The brain regions identified have been linked to a neural endophenotype that confers vulnerability to obesity, suggesting a genetically-based hypersensitivity to food-associated images and smells.
"Obesity is becoming more common around the world and it's well known to cause health problems such as heart disease and diabetes," says Dr. Dagher. "This study describes the mechanism through which ghrelin makes people more vulnerable to hunger-causing stimuli, and the more we know about this, the easier it will be to develop therapies that counteract this effect."
https://www.sciencedaily.com/releases/2018/12/181212121907.htm
New insight into aging
Plasticity is enhanced but dysregulated in the aging brain
September 19, 2018
Science Daily/McGill University
Researchers examined the effects of aging on neuroplasticity in the primary auditory cortex, the part of the brain that processes auditory information. Neuroplasticity refers to the brain's ability to modify its connections and function in response to environmental demands, an important process in learning.
They say you can't teach old dogs new tricks, but new research shows you can teach an old rat new sounds, even if the lesson doesn't stick very long.
Researchers at the Montreal Neurological Institute and Hospital (The Neuro) of McGill University examined the effects of aging on neuroplasticity in the primary auditory cortex, the part of the brain that processes auditory information. Neuroplasticity refers to the brain's ability to modify its connections and function in response to environmental demands, an important process in learning.
Plasticity in the young brain is very strong as we learn to map our surroundings using the senses. As we grow older, plasticity decreases to stabilize what we have already learned. This stabilization is partly controlled by a neurotransmitter called gamma-Aminobutyric acid (GABA), which inhibits neuronal activity. This role of GABA was discovered by K.A.C. Elliot and Ernst Florey at The Neuro in 1956.
First author Dr. Mike Cisneros-Franco and lab director Dr. Étienne de Villers-Sidani wanted to test the hypothesis that plasticity stabilization processes become dysregulated as we age. They ran an experiment where rats were exposed to audio tones of a specific frequency to measure how neurons in the primary auditory cortex adapt their responses to the tones.
They found that tone exposure caused neurons in older adult rats to become increasingly sensitized to the frequency, but this did not happen in younger adult rats. The effect in the older adult rats quickly disappeared after exposure, showing that plasticity was indeed dysregulated. However, by increasing the levels of the GABA neurotransmitter in another group of older rats, the exposure-induced plastic changes in the auditory cortex lasted longer.
These findings suggest the brain's ability to adapt its functional properties does not disappear as we age. Rather, they provide evidence that plasticity is, in fact, increased but dysregulated in the aged brain because of reduced GABA levels. Overall, the findings suggest that increasing GABA levels may improve the retention of learning in the aging brain.
"Our work showed that the aging brain is, contrary to a widely-held notion, more plastic than the young adult brain," says Cisneros-Franco. "On the flip side, this increased plasticity meant that any changes achieved through stimulation or training were unstable: both easy to achieve and easy to reverse."
"However, we also showed that it is possible to reduce this instability using clinically available drugs. Researchers and clinicians may build upon this knowledge to develop rehabilitation strategies to harness the full plastic potential of the aging brain."
https://www.sciencedaily.com/releases/2018/09/180919115827.htm