Bi-directional communication between neurons and astrocytes modulates spinal motor circuits

Matthew James Broadhead; Gareth Brian Miles

doi:10.3389/fncel.2020.00030

Bi-directional communication between neurons and astrocytes modulates spinal motor circuits

Matthew James Broadhead, Gareth Brian Miles

Research output: Contribution to journal › Article › peer-review

Abstract

Evidence suggests that astrocytes are not merely supportive cells in the nervous system but may actively participate in the control of neural circuits underlying cognition and behavior. In this study, we examined the role of astrocytes within the motor circuitry of the mammalian spinal cord. Pharmacogenetic manipulation of astrocytic activity in isolated spinal cord preparations obtained from neonatal mice revealed astrocyte-derived, adenosinergic modulation of the frequency of rhythmic output generated by the locomotor central pattern generator (CPG) network. Live Ca²⁺ imaging demonstrated increased activity in astrocytes during locomotor-related output and in response to the direct stimulation of spinal neurons. Finally, astrocytes were found to respond to neuronally-derived glutamate in a metabotropic glutamate receptor 5 (mGluR5) dependent manner, which in turn drives astrocytic modulation of the locomotor network. Our work identifies bi-directional signaling mechanisms between neurons and astrocytes underlying modulatory feedback control of motor circuits, which may act to constrain network output within optimal ranges for movement.

Original language	English
Article number	30
Number of pages	14
Journal	Frontiers in Cellular Neuroscience
Volume	14
DOIs	https://doi.org/10.3389/fncel.2020.00030
Publication status	Published - 27 Feb 2020

Keywords

Astrocyte
Spinal cord
Locomotion
Neuromodulation
mGlu receptor5

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10.3389/fncel.2020.00030Licence: CC BY

Broadhead_2020_FCN_Bi-directional_CC
Copyright © 2020 Broadhead and Miles. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Final published version, 5.36 MBLicence: CC BY

Glial Cell Involvement: Glial cell involvement in spinal motor control: cheering from the side-lines or part of the team.
Miles, G. B. (PI) & Pulver, S. R. (CoI)
BBSRC
15/12/15 → 14/12/18
Project: Standard

Cite this

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title = "Bi-directional communication between neurons and astrocytes modulates spinal motor circuits",

abstract = "Evidence suggests that astrocytes are not merely supportive cells in the nervous system but may actively participate in the control of neural circuits underlying cognition and behavior. In this study, we examined the role of astrocytes within the motor circuitry of the mammalian spinal cord. Pharmacogenetic manipulation of astrocytic activity in isolated spinal cord preparations obtained from neonatal mice revealed astrocyte-derived, adenosinergic modulation of the frequency of rhythmic output generated by the locomotor central pattern generator (CPG) network. Live Ca2+ imaging demonstrated increased activity in astrocytes during locomotor-related output and in response to the direct stimulation of spinal neurons. Finally, astrocytes were found to respond to neuronally-derived glutamate in a metabotropic glutamate receptor 5 (mGluR5) dependent manner, which in turn drives astrocytic modulation of the locomotor network. Our work identifies bi-directional signaling mechanisms between neurons and astrocytes underlying modulatory feedback control of motor circuits, which may act to constrain network output within optimal ranges for movement.",

keywords = "Astrocyte, Spinal cord, Locomotion, Neuromodulation, mGlu receptor5",

author = "Broadhead, {Matthew James} and Miles, {Gareth Brian}",

note = "Funding was provided by the Biotechnology and Biological Science Research Grant (BB/M021793/1), the Motor Neurone Disease (MND) Association UK and the RS MacDonald Charitable Trust.",

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AU - Broadhead, Matthew James

AU - Miles, Gareth Brian

N1 - Funding was provided by the Biotechnology and Biological Science Research Grant (BB/M021793/1), the Motor Neurone Disease (MND) Association UK and the RS MacDonald Charitable Trust.

PY - 2020/2/27

Y1 - 2020/2/27

N2 - Evidence suggests that astrocytes are not merely supportive cells in the nervous system but may actively participate in the control of neural circuits underlying cognition and behavior. In this study, we examined the role of astrocytes within the motor circuitry of the mammalian spinal cord. Pharmacogenetic manipulation of astrocytic activity in isolated spinal cord preparations obtained from neonatal mice revealed astrocyte-derived, adenosinergic modulation of the frequency of rhythmic output generated by the locomotor central pattern generator (CPG) network. Live Ca2+ imaging demonstrated increased activity in astrocytes during locomotor-related output and in response to the direct stimulation of spinal neurons. Finally, astrocytes were found to respond to neuronally-derived glutamate in a metabotropic glutamate receptor 5 (mGluR5) dependent manner, which in turn drives astrocytic modulation of the locomotor network. Our work identifies bi-directional signaling mechanisms between neurons and astrocytes underlying modulatory feedback control of motor circuits, which may act to constrain network output within optimal ranges for movement.

AB - Evidence suggests that astrocytes are not merely supportive cells in the nervous system but may actively participate in the control of neural circuits underlying cognition and behavior. In this study, we examined the role of astrocytes within the motor circuitry of the mammalian spinal cord. Pharmacogenetic manipulation of astrocytic activity in isolated spinal cord preparations obtained from neonatal mice revealed astrocyte-derived, adenosinergic modulation of the frequency of rhythmic output generated by the locomotor central pattern generator (CPG) network. Live Ca2+ imaging demonstrated increased activity in astrocytes during locomotor-related output and in response to the direct stimulation of spinal neurons. Finally, astrocytes were found to respond to neuronally-derived glutamate in a metabotropic glutamate receptor 5 (mGluR5) dependent manner, which in turn drives astrocytic modulation of the locomotor network. Our work identifies bi-directional signaling mechanisms between neurons and astrocytes underlying modulatory feedback control of motor circuits, which may act to constrain network output within optimal ranges for movement.

KW - Astrocyte

KW - Spinal cord

KW - Locomotion

KW - Neuromodulation

KW - mGlu receptor5

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DO - 10.3389/fncel.2020.00030

M3 - Article

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VL - 14

JO - Frontiers in Cellular Neuroscience

JF - Frontiers in Cellular Neuroscience

M1 - 30

ER -

Bi-directional communication between neurons and astrocytes modulates spinal motor circuits

Abstract

Keywords

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Glial Cell Involvement: Glial cell involvement in spinal motor control: cheering from the side-lines or part of the team.

Cite this