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Astrocyte glutamate transport is modulated by motor learning and regulates neuronal correlations and movement encoding by motor cortex neurons

View ORCID ProfileChloe Delepine, Keji Li, Jennifer Shih, Pierre Gaudeaux, View ORCID ProfileMriganka Sur
doi: https://doi.org/10.1101/2022.01.20.477039
Chloe Delepine
1Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
2Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
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Keji Li
1Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
2Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
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Jennifer Shih
1Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
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Pierre Gaudeaux
1Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
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Mriganka Sur
1Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
2Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
3Simons Center for the Social Brain, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA
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  • For correspondence: msur@mit.edu
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ABSTRACT

While motor cortex is crucial for learning precise and reliable movements, whether and how astrocytes contribute to its plasticity and function during motor learning is unknown. Here we report that primary motor cortex (M1) astrocytes in mice show in vivo plasticity during learning of a lever push task, as revealed by transcriptomic and functional modifications. In particular, we observe changes in expression of glutamate transporter genes and increased coincidence of intracellular calcium events. Astrocyte-specific manipulations of M1 are sufficient to alter motor learning and execution, and neuronal population coding, in the same task. Mice expressing decreased levels of the astrocyte glutamate transporter GLT1 show impaired and variable movement trajectories. Mice with increased astrocyte Gq signaling show decreased performance rates, delayed response times and impaired trajectories, along with abnormally high levels of GLT1. In both groups of mice, M1 neurons have altered inter-neuronal correlations and impaired population representations of task parameters, including response time and movement trajectories. Thus, astrocytes have a specific role in coordinating M1 neuronal activity during motor learning, and control learned movement execution and dexterity through mechanisms that importantly include fine regulation of glutamate transport.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted January 21, 2022.
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Astrocyte glutamate transport is modulated by motor learning and regulates neuronal correlations and movement encoding by motor cortex neurons
Chloe Delepine, Keji Li, Jennifer Shih, Pierre Gaudeaux, Mriganka Sur
bioRxiv 2022.01.20.477039; doi: https://doi.org/10.1101/2022.01.20.477039
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Astrocyte glutamate transport is modulated by motor learning and regulates neuronal correlations and movement encoding by motor cortex neurons
Chloe Delepine, Keji Li, Jennifer Shih, Pierre Gaudeaux, Mriganka Sur
bioRxiv 2022.01.20.477039; doi: https://doi.org/10.1101/2022.01.20.477039

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