Astrocyte cells critical for learning skilled movements

From steering a car to swinging a tennis racket, we learn to execute all kinds of skilled movements during our lives. You might think this learning is only implemented by neurons, but a new study by researchers at The Picower Institute for Learning and Memory at MIT shows the essential role of another brain cell type: astrocytes.

Just as teams of elite athletes train alongside staffs of coaches, ensembles of neurons in the brain's motor cortex depend on nearby astrocytes to help them learn to encode when and how to move, and the optimal timing and trajectory of a motion, the study shows. Describing a series of experiments in mice, the new paper in the Journal of Neuroscience reveals two specific ways that astrocytes directly impact motor learning, maintaining an optimal molecular balance in which the neuronal ensembles can properly refine movement performance.

"This finding is part of a body of work from our lab and other labs that elevate the importance of astrocytes to neuronal encoding and hence to behavior," said senior author Mriganka Sur, Newton Professor of Neuroscience in The Picower Institute and MIT's Department of Brain and Cognitive Sciences. "This shows that while the population coding of behaviors is a neuronal function, we need to include astrocytes as partners with them."

Picower Institute Postdoc Jennifer Shih and former Sur Lab postdocs Chloe Delepine and Keji Li are the paper's co-lead authors.

"This research highlights the complexity of astrocytes and the importance of astrocyte-neuron interactions in fine-tuning brain function by providing concrete evidence of these mechanisms in the motor cortex," Delepine said.

Messing with motor mastery

The team gave their mice a simple motor task to master. When cued with a tone, the mice had to reach for and push down a lever within five seconds. The rodents showed they could learn the task over a few days and master it within a couple of weeks. They not only performed the task more accurately, but also their reactions quickened and the trajectory of their reaching and pushing became smoother and more uniform.

In some of the mice, however, the team employed precision molecular interventions to disrupt two specific functions of astrocytes in the motor cortex. In some mice, they disrupted the astrocytes' ability to soak up the neurotransmitter glutamate, a chemical that excites neural activity when it is received at connections called synapses. In other mice they hyperactivated the astrocytes' calcium signals, which affected how they function. In both ways, the interventions disrupted the normal process by which neurons would form or change their connections with each other, a process called "plasticity" that enables learning.

The interventions each affected the performance of the mice. The first one (a knockdown of the glutamate transporter GLT1) didn't affect whether the mice pushed the lever or how quickly they did so. Instead it disrupted the smoothness of the motion. Mice with GLT1 disrupted remained erratic and shaky, as if unable to refine their technique. Mice subjected to the second intervention (activation of Gq signaling) showed deficits not only in the smoothness of their motion trajectory but also in their understanding of when to push the lever and their quickness in doing so.

The team dug deeper into how these deficits emerged. Using a two-photon microscope they tracked neural activity in the motor cortex in unaltered mice and mice treated with each intervention. Compared to what they saw in normal mice, the mice with GLT1 disrupted showed less correlated activity among neurons. Mice with Gq activation showed excessive correlated activity compared to the normal mice.

"The data suggest that an optimal level of neuronal correlation is required for the emergence of functional neuronal ensembles that drive task performance," the authors wrote. "Meaningful correlations that carry information are what drive motor learning rather than the absolute magnitude of potentially non-specific correlations."

The team dug even deeper still. They carefully isolated astrocytes from the motor cortex of mice, including some who were untrained in the motor task as well as ones who were trained, including mice who were unaltered and mice who underwent each intervention. In all these samples of purified astrocytes, they then sequenced RNA to assess how they differed in their expression of genes. They found that in trained vs. untrained mice, astrocytes exhibited greater expression of genes related to GLT1. In mice where they intervened they saw lowered expression. That evidence further suggested that the glutamate transporter process is indeed fundamental to training in motor tasks.

"Here we show that astrocytes have an important role in enabling neurons to encode information properly, both the learning and the execution of a movement for example," Sur said.

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Scientists key in on brain’s mechanism for singing, learning

New research reveals that specialized cells within neural circuitry that triggers complex learning in songbirds bears a striking resemblance to a type of neural cell associated with the development of fine motor skills in the cortex of the human brain.

The study by scientists at Oregon Health & Science University published today in the journal Nature Communications.

"These are the properties you need if you want to have a male song that's precise and distinct so the female can choose which bird she wants to mate with," said co-senior author Henrique von Gersdorff, Ph.D., senior scientist the OHSU Vollum Institute. "You need a highly specialized brain to produce this."

Benjamin Zemel, Ph.D., a postdoctoral fellow at OHSU, is lead author and conducted most of the challenging electrophysiology work involved in using thin brain slices and single cell recording.

The study reveals that a particular group of neurons express a set of genes that modulate sodium ion channel proteins. These ion channels generate electrical signals used for communication between cells in the nervous system. In this case, the assemblage enables neurons to fire repetitive spikes - known as action potentials - at extremely high speeds and frequencies as the bird sings.

The study describes "ultrafast spikes" that only last 0.2 milliseconds - compared with most action potential spikes that last a millisecond or more. A millisecond is itself mind-bendingly fast, a thousandth of a second.

Further, the findings suggest new avenues for understanding the mechanism in various aspects of human behavior and development that involves fine motor control.

Researchers say the assemblage of neurons and ion channels involved in the male zebra finch's singing closely resembles a similar assemblage of neurons known as Betz cells in the primary motor cortex of the human brain.

Among the largest known brain cells in humans, Betz cells have long and thick axons that can propagate spikes at very high velocities and frequencies. As such, they are thought to be important for fine motor skills involving hands, feet, fingers and wrists.

"Think of a piano player," said co-senior author Claudio Mello, M.D., Ph.D., professor of behavioral neuroscience in the OHSU School of Medicine. "They're thinking so fast, they have to rely on memories and actions that are learned and stored. Playing the guitar is the same thing."

The study published today is a result of an informal conversation that initially occurred over lunch in the Mackenzie Hall Café on OHSU's Marquam Hill campus.

Mello, a behavioral neuroscientist who has relied on the zebra finch as an animal model, has known Von Gersdorff socially for 20 years. Over lunch one day in the cafeteria, Mello popped open his laptop and showed a brain image of a young male zebra finch at an age just before he could sing, followed by a second image revealing a telltale subunit of proteins that had materialized after the bird was old enough to begin singing.

"Something remarkable was happening in a period of just a few days," said von Gersdorff, an expert in electrophysiology and the biophysics of neurons. "I said, this is exactly the protein we've been studying in the rodent auditory system. It promotes high frequency spiking."

Mello said the new study deepens scientific understanding of the mechanism involved in learning fine motor skills.

"This is a very important model, and we think this new study has broad potential," he said.

The fact that these same motor circuit properties are shared by species that diverged more than 300 million years ago speaks to the strength of the discovery, von Gersdorff and Mello said. Researchers say the neuronal properties they discovered in the male zebra finch may become optimized for speed and precision through convergent evolution.

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Children's temperament traits affect their motor skills

A recent study among 3- to 7-year-old children showed that children's motor skills benefitted if a child was older and participated in organised sports. Additionally, the study provided information about the importance of temperament traits for motor skills. More specifically, traits such as activity and attention span persistence were found to be positively associated with motor skills. This was a rather novel result, as the association between motor skills and temperament during early childhood is not yet widely understood.

In essence, motor skills comprise locomotor, ball and balance skills, all of which are present in everyday life tasks like running, climbing, throwing and drawing. Adequate motor skills enable participation in typical games and types of playing for different ages and developmental phases, for example, in tag, running and ball games.

"Even though motor skills develop as a function of age, skill development still needs to be stimulated consciously," says Donna Niemistö, a PhD student from the Faculty of Sport and Health Sciences, University of Jyväskylä. "Motor skills do not develop without practising, thus skills need reinforcement through repetition of the skills. Motor skill development is greatly supported when the child is moving in multiple ways. In a current study we found more evidence that participation in organised sports can be useful to gain more opportunities to practise and repeat essential movements."

Temperament and its traits refer to a child's biological and individual characteristics, such as the biological way of reacting to one's surroundings. Temperament is rather stable over time. To date, there have been only a handful of studies concerning young children's motor skills and temperament traits, even though in older age groups, more research is already available.

"Children who tend to have an active type of temperament, as well as children who show persistency when faced with challenges can be motivated and persistent in learning and rehearsing motor tasks. Therefore, these findings were expected and logical. A child with an active temperament can react more rapidly. Consequently, the child will get more opportunities to move along with increased repetitions. Without noticing, the child will also gain more opportunities to perform motor tasks."

Additionally, the capacity to maintain attention is equally important for skill acquisition.

"To learn new skills, one must be able to concentrate and maintain focus even though the skill may, at first, feel challenging or even difficult," continues Niemistö.

Both temperament traits can influence the development of motor skills. Therefore, it is important that parents as well as early educators and teachers are aware of these individual factors in case they want to encourage and support their children's motor skill development.

"For example, there is no need to emphasize for an active child to be more active," Niemistö explains. "However, with an active child, a parent could guide the child to maintain focus and attention, despite possible distractions in the surroundings."

Motor skills were assessed with two internationally well-known measurements. The first assessment tool measured the locomotor and ball skills and the second one the balance and coordination skills of the child. As the chosen assessment tools measured divergent aspects of motor development, differences between associated factors related to motor skills were also found.

"The development of balance and coordination skills was better in those children who were described as more emotionally regulated," says Niemistö. "On the other hand, locomotor skills were better in children whose parents had higher educational level and the development of ball skills benefitted if children had free access to sport facilities in nearby surroundings."

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