Rapid modulation of striatal cholinergic interneurons and dopamine release by satellite astrocytes

Abstract Astrocytes are increasingly appreciated to possess underestimated and important roles in modulating neuronal circuits. Astrocytes in striatum can regulate dopamine transmission by governing the extracellular tone of axonal neuromodulators, including GABA and adenosine. However, here we reve...

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Main Authors: Jeffrey Stedehouder, Bradley M. Roberts, Shinil Raina, Simon Bossi, Alan King Lun Liu, Natalie M. Doig, Kevin McGerty, Peter J. Magill, Laura Parkkinen, Stephanie J. Cragg
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-54253-7
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author Jeffrey Stedehouder
Bradley M. Roberts
Shinil Raina
Simon Bossi
Alan King Lun Liu
Natalie M. Doig
Kevin McGerty
Peter J. Magill
Laura Parkkinen
Stephanie J. Cragg
author_facet Jeffrey Stedehouder
Bradley M. Roberts
Shinil Raina
Simon Bossi
Alan King Lun Liu
Natalie M. Doig
Kevin McGerty
Peter J. Magill
Laura Parkkinen
Stephanie J. Cragg
author_sort Jeffrey Stedehouder
collection DOAJ
description Abstract Astrocytes are increasingly appreciated to possess underestimated and important roles in modulating neuronal circuits. Astrocytes in striatum can regulate dopamine transmission by governing the extracellular tone of axonal neuromodulators, including GABA and adenosine. However, here we reveal that striatal astrocytes occupy a cell type-specific anatomical and functional relationship with cholinergic interneurons (ChIs), through which they rapidly excite ChIs and govern dopamine release via nicotinic acetylcholine receptors on subsecond timescales. We identify that ChI somata are in unexpectedly close proximity to astrocyte somata, in mouse and human, forming a “soma-to-soma” satellite-like configuration not typically observed for other striatal neurons. We find that transient depolarization of astrocytes in mouse striatum reversibly regulates ChI excitability by decreasing extracellular calcium. These findings reveal a privileged satellite astrocyte-interneuron interaction for striatal ChIs operating on subsecond timescales via regulation of extracellular calcium dynamics to shape downstream striatal circuit activity and dopamine signaling.
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spelling doaj-art-6aeb3ac2bdaf4b678bd9203fe41e062b2024-11-24T12:34:40ZengNature PortfolioNature Communications2041-17232024-11-0115111710.1038/s41467-024-54253-7Rapid modulation of striatal cholinergic interneurons and dopamine release by satellite astrocytesJeffrey Stedehouder0Bradley M. Roberts1Shinil Raina2Simon Bossi3Alan King Lun Liu4Natalie M. Doig5Kevin McGerty6Peter J. Magill7Laura Parkkinen8Stephanie J. Cragg9Centre for Cellular and Molecular Neurobiology, Department of Physiology, Anatomy and Genetics, University of OxfordCentre for Cellular and Molecular Neurobiology, Department of Physiology, Anatomy and Genetics, University of OxfordCentre for Cellular and Molecular Neurobiology, Department of Physiology, Anatomy and Genetics, University of OxfordCentre for Cellular and Molecular Neurobiology, Department of Physiology, Anatomy and Genetics, University of OxfordOxford Parkinson’s Disease Centre, University of OxfordAligning Science Across Parkinson’s (ASAP) Collaborative Research NetworkMathematical Institute, University of OxfordOxford Parkinson’s Disease Centre, University of OxfordOxford Parkinson’s Disease Centre, University of OxfordCentre for Cellular and Molecular Neurobiology, Department of Physiology, Anatomy and Genetics, University of OxfordAbstract Astrocytes are increasingly appreciated to possess underestimated and important roles in modulating neuronal circuits. Astrocytes in striatum can regulate dopamine transmission by governing the extracellular tone of axonal neuromodulators, including GABA and adenosine. However, here we reveal that striatal astrocytes occupy a cell type-specific anatomical and functional relationship with cholinergic interneurons (ChIs), through which they rapidly excite ChIs and govern dopamine release via nicotinic acetylcholine receptors on subsecond timescales. We identify that ChI somata are in unexpectedly close proximity to astrocyte somata, in mouse and human, forming a “soma-to-soma” satellite-like configuration not typically observed for other striatal neurons. We find that transient depolarization of astrocytes in mouse striatum reversibly regulates ChI excitability by decreasing extracellular calcium. These findings reveal a privileged satellite astrocyte-interneuron interaction for striatal ChIs operating on subsecond timescales via regulation of extracellular calcium dynamics to shape downstream striatal circuit activity and dopamine signaling.https://doi.org/10.1038/s41467-024-54253-7
spellingShingle Jeffrey Stedehouder
Bradley M. Roberts
Shinil Raina
Simon Bossi
Alan King Lun Liu
Natalie M. Doig
Kevin McGerty
Peter J. Magill
Laura Parkkinen
Stephanie J. Cragg
Rapid modulation of striatal cholinergic interneurons and dopamine release by satellite astrocytes
Nature Communications
title Rapid modulation of striatal cholinergic interneurons and dopamine release by satellite astrocytes
title_full Rapid modulation of striatal cholinergic interneurons and dopamine release by satellite astrocytes
title_fullStr Rapid modulation of striatal cholinergic interneurons and dopamine release by satellite astrocytes
title_full_unstemmed Rapid modulation of striatal cholinergic interneurons and dopamine release by satellite astrocytes
title_short Rapid modulation of striatal cholinergic interneurons and dopamine release by satellite astrocytes
title_sort rapid modulation of striatal cholinergic interneurons and dopamine release by satellite astrocytes
url https://doi.org/10.1038/s41467-024-54253-7
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