Astrocyte cells essential for learning skilled movements

Summary: The study reveals two specific ways in which astrocytes directly impact motor learning.

Source: Picower Institute for Learning and Memory

From driving a car to swinging a tennis racket, we learn to perform all sorts of skillful moves over the course of our lives. You might think that this learning is only carried out by neurons, but a new study by researchers at MIT’s Picower Institute for Learning and Memory shows the essential role of another type of cell cerebral: astrocytes.

Just as teams of elite athletes train alongside coaches, sets of neurons in the motor cortex of the brain depend on nearby astrocytes to help them learn to code when and how to move, as well as the optimal timing and trajectory of a movement, according to the study.

Describing a series of experiments on mice, the new article from the Journal of Neuroscience reveals two specific ways in which astrocytes directly impact motor learning, maintaining an optimal molecular balance in which neural ensembles can properly fine-tune movement performance.

“This finding is part of a body of work from our lab and other labs that elevates the importance of astrocytes to neural coding and therefore behavior,” said lead author Mriganka Sur, Newton Professor of Neuroscience at the Picower Institute and MIT’s Department of the Brain. and cognitive science.

“This shows that if population coding of behaviors is a neural function, we need to include astrocytes as partners.”

Jennifer Shih, post-doctoral fellow at the Picower Institute, and former Sur Lab post-doctoral fellows, Chloe Del├ępine and Keji Li, are the co-lead authors of the article.

“This research highlights the complexity of astrocytes and the importance of astrocyte-neuron interactions in fine-tuning brain function by providing concrete evidence for these mechanisms in the motor cortex,” Del├ępine said.

Playing with motor skills

The team gave their mice a simple motor task to master. When alerted by a tone, the mice had to reach and lower a lever within five seconds. Rodents were shown to be able to learn the task within days and master it within weeks. Not only did they perform the task more accurately, but their reactions quickened and the trajectory of their reach and thrust became smoother and more even.

In some mice, however, the team used precision molecular interventions to disrupt two specific functions of astrocytes in the motor cortex. In some mice, they disrupted the ability of astrocytes to take up the neurotransmitter glutamate, a chemical that excites neuronal activity when received at connections called synapses.

In other mice, they hyperactivated the calcium signals of astrocytes, which affected their functioning. In both directions, the interventions disrupted the normal process by which neurons would form or change their connections to each other, a process called “plasticity” that enables learning.

The interventions each affected the performance of the mice. The first (a knockdown of the glutamate transporter GLT1) did not affect whether the mice pushed the lever or how fast they did so. Instead, it disrupted the fluidity of movement.

Mice with disrupted GLT1 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 movement trajectory, but also in their understanding of when to push the lever and their speed in doing so.

It shows a brain
This evidence further suggests that the process of glutamate transport is indeed fundamental to motor task training. Image is in public domain

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

“The data suggest that an optimal level of neural correlation is necessary for the emergence of functional neural ensembles that drive task execution,” 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. They carefully isolated astrocytes from the motor cortex of mice, including some that were not trained on the motor task as well as those that were trained, including mice that were not modified and mice that underwent each action. In all of these purified astrocyte samples, they then sequenced the RNA to assess how they differed in their gene expression.

They found that in trained mice compared to untrained mice, astrocytes showed greater expression of GLT1-related genes. In mice where they intervened, they saw reduced expression. This evidence further suggests that the process of glutamate transport is indeed fundamental to motor task training.

“Here we show that astrocytes play an important role in allowing neurons to correctly encode information, both learning and executing a movement for example,” Sur said.

Pierre Gaudeaux is co-author of the article.

Funding: The research was funded by the National Institutes of Health, the Simons Foundation and the JPB Foundation.

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About this Motor Learning Research News

Author: David Orenstein
Source: Picower Institute of Learning and Memory
Contact: David Orenstein – Picower Institute of Learning and Memory
Picture: Image is in public domain

Original research: Access closed.
“Differential effects of astrocyte manipulations on learned motor behavior and neural ensembles in the motor cortex” by Mriganka Sur et al. Journal of Neuroscience


Abstract

Differential effects of astrocyte manipulations on learned motor behavior and neural ensembles in the motor cortex

While the motor cortex is crucial for learning precise and reliable movements, it is unknown if and how astrocytes contribute to its plasticity and function during motor learning.

Here, we report that astrocyte-specific manipulations in the primary motor cortex (M1) during a lever-pushing task alter motor learning and execution, as well as the coding of the underlying neuronal population.

Mice that express reduced levels of the astrocyte glutamate transporter GLT1 exhibit impaired and variable movement trajectories, whereas mice with increased astrocyte Gq signaling exhibit reduced performance rates, delayed response times, and impaired trajectories.

In both groups, which include both male and female mice, M1 neurons have altered inter-neuronal correlations and altered population representations of task parameters, including response time and movement trajectories.

RNA sequencing further supports the role of M1 astrocytes in motor learning and shows changes in astrocyte expression of glutamate transporter genes, GABA transporter genes, and extracellular matrix protein genes in mice. who have acquired this learned behavior.

Thus, astrocytes coordinate M1 neuronal activity during motor learning, and our results suggest that this contributes to learned movement execution and dexterity through mechanisms that include regulation of neurotransmitter transport and signaling. calcium.

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