From driving a car to swinging a tennis racket, we learn to perform all kinds of skillful movements throughout 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 brain cell: astrocytes.
The study showed that just as teams of elite athletes train alongside coaches, groups of neurons in the brain’s motor cortex rely on nearby astrocytes to help them learn to encode when and how to move, and the optimal timing and path of movement. describing a series of experiments on rats in the new paper Journal of Neuroscience It reveals two specific ways in which astrocytes directly influence motor learning, maintaining optimal molecular homeostasis in which neuronal populations can properly optimize motor performance.
This finding is part of a body of work from our lab and others that raise the importance of astrocytes in neuronal coding and thus in behavior. This shows that while population coding of behavior is a neuronal function, we need to include astrocytes as their partners.”
Mriganka Sur, S.;junior author, Newton Professor of Neuroscience at the Piccoer Institute and the Department of Brain and Cognitive Sciences at MIT
The paper was co-authored by Jennifer Shih, Picower Institute Postdoc, and former Sur Lab postdocs Chloe Delbin and Keiji Lee.
“This research highlights the complexity of astrocytes and the importance of the interactions of astrocytes with neurons in modulating brain function by providing concrete evidence of these mechanisms in the motor cortex,” Delbin said.
Messing with engine mastery
The team gave the mice a simple motor task to master. Upon sounding a tone, the rats had to reach out and push down within five seconds. The rodents have shown that they can learn the task in a few days and master it in two weeks. Not only did they perform the task more accurately, but their reflexes quickened and their reach and thrust trajectory became smoother and more uniform.
However, in some mice the team used precise 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 triggers neural activity when it’s received through connections called synapses. In other mice they activated calcium signaling to astrocytes, affecting how they function. In both directions, the interventions disrupted the natural process by which neurons can form or change their connections with one another, a process called “plasticity” that enables learning.
Both interventions affected the performance of the mice. The first (knockdown of the glutamate transporter GLT1) did not affect whether or how quickly the mice pushed the lever. Instead, disable Smooth Motion. GLT1-deficient mice remained erratic and shivering, as if unable to improve their technique. Mice subjected to the second intervention (activation of Gq signaling) showed defects not only in the smoothness of their locomotion trajectory but also in their understanding of when to push the lever and their speed in doing so.
The team delved into how this deficit manifests itself. Using a two-photon microscope, they tracked neural activity in the motor cortex of rats and mice that did not change with each intervention. Compared to what they saw in normal mice, the GLT1-deficient mice showed less correlative activity between neurons. Mice with Gq activation showed excessive correlative activity compared to normal mice.
“The data suggest that an optimal level of neural connectivity is required for the emergence of functional neural populations that drive task performance,” the authors wrote. “It is the meaningful associations that carry information that drive motor learning rather than the absolute magnitude of potential non-specific associations.”
The team dug even deeper. They carefully isolated astrocytes from the motor cortex of mice, including some that had not been trained on motor tasks as well as those that had been trained, including unchanged mice and mice that had undergone each intervention. In all of these samples of purified astrocytes, they then sequenced their RNA to assess how differently they expressed genes. They found that in trained versus untrained mice, astrocytes showed greater expression of GLT1-related genes. In the mice they entered, they saw reduced expression. This evidence also indicates that glutamate transmission is indeed central to training for motor tasks.
“We show here that astrocytes have an important role in enabling neurons to correctly encode information, whether in learning or executing movement for example,” Sohr said.
Pierre Godot is a co-author of the paper. The research was funded by the National Institutes of Health, the Simmons Foundation, and the JPB Foundation.
Delpin, C., et al. (2023) Differential effects of astrocyte manipulation on learned motor behavior and neuronal groups in the motor cortex. Journal of Neuroscience. doi.org/10.1523/JNEUROSCI.1982-22.2023.