Astrocyte cells have been found to play a critical role in learning skilled movements. Astrocytes are a type of glial cell in the brain that provide support and nourishment to neurons. Recent studies have shown that they also play an active role in regulating neural activity and synaptic plasticity, which are important mechanisms for learning and memory.
A new study in mice reveals that when astrocyte function is disrupted, neurons in the brain’s motor cortex struggle to execute and refine motion. We learn to perform a variety of skilled movements throughout our lives, from driving a car to swinging a tennis racket. You might think that neurons are the only ones who implement this learning, but a new study from The Picower Institute for Learning and Memory at MIT shows that astrocytes play an important role as well.
According to the study, just as elite athletes train alongside coaching staffs, ensembles of neurons in the brain’s motor cortex rely on nearby astrocytes to help them learn to encode when and how to move, as well as the optimal timing and trajectory of a motion. The new paper in the Journal of Neuroscience describes a series of experiments in mice that reveal two specific ways that astrocytes directly impact motor learning, maintaining an optimal molecular balance in which neuronal ensembles can properly refine movement performance.
“This finding adds to a body of work from our lab and other labs that emphasizes the importance of astrocytes to neuronal encoding and thus to behavior,” said senior author Mriganka Sur, Newton Professor of Neuroscience at The Picower Institute and MIT’s Department of Brain and Cognitive Sciences. “This demonstrates that, while population coding of behaviors is a neuronal function, astrocytes must be included as partners.”
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.Chloe Delepine
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 mice were given a simple motor task to master by the team. The mice had five seconds after hearing a tone to reach for and push down a lever. The rodents demonstrated that they could learn the task in a few days and master it in a couple of weeks. They not only completed the task more accurately, but their reactions also became faster, and the trajectory of their reaching and pushing became smoother and more uniform.
However, in some of the mice, the researchers used precision molecular interventions to disrupt two distinct functions of astrocytes in the motor cortex. They interfered with the ability of astrocytes to absorb the neurotransmitter glutamate, a chemical that stimulates neural activity when it is received at synapses. They hyperactivated the calcium signals of astrocytes in other mice, affecting how they functioned. Both interventions disrupted the normal process by which neurons form or change their connections with one another, a process known as “plasticity” that allows learning.
Each intervention had an effect on the mice’s performance. The first (a knockdown of the glutamate transporter GLT1) had no effect on whether or not the mice pushed the lever. Instead, it disrupted the motion’s smoothness. Mice lacking GLT1 remained erratic and shaky, as if unable to fine-tune their technique. Mice exposed to the second intervention (activation of Gq signaling) demonstrated deficits not only in the smoothness of their motion trajectory, but also in their understanding of when to push the lever and their speed in doing so.
The team dug deeper into the causes of these deficiencies. They tracked neural activity in the motor cortex of unaltered mice and mice treated with each intervention using a two-photon microscope. When compared to normal mice, the mice with GLT1 disruption showed less correlated activity among neurons. Mice with Gq activation had higher levels of correlated activity than normal mice.
The findings “suggest that an optimal level of neuronal correlation is required for the emergence of functional neuronal ensembles that drive task performance,” the researchers wrote. “Rather than the absolute magnitude of potentially non-specific correlations, meaningful correlations that carry information drive motor learning.”
The team dug even deeper. They carefully isolated astrocytes from the motor cortex of mice, including those that were untrained in the motor task as well as those that were trained, as well as mice that were unaltered and mice that underwent each intervention. They then sequenced RNA from all of these purified astrocyte samples to see how they differed in gene expression. They discovered that in trained vs. untrained mice, astrocytes expressed more GLT1-related genes. They observed reduced expression in mice where they intervened. This evidence suggested that the glutamate transporter process is indeed essential for motor task training.