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Astrocytes—The Ultimate Effectors of Long-Range Neuromodulatory Networks?

It was long thought that astrocytes, given their lack of electrical signaling, were not involved in communication with neurons. However, we now know that one astrocyte on average maintains and regulates the extracellular neurotransmitter and potassium levels of more than 140,000 synapses, both excit...

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Autores principales: Pacholko, Anthony G., Wotton, Caitlin A., Bekar, Lane K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554522/
https://www.ncbi.nlm.nih.gov/pubmed/33192327
http://dx.doi.org/10.3389/fncel.2020.581075
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author Pacholko, Anthony G.
Wotton, Caitlin A.
Bekar, Lane K.
author_facet Pacholko, Anthony G.
Wotton, Caitlin A.
Bekar, Lane K.
author_sort Pacholko, Anthony G.
collection PubMed
description It was long thought that astrocytes, given their lack of electrical signaling, were not involved in communication with neurons. However, we now know that one astrocyte on average maintains and regulates the extracellular neurotransmitter and potassium levels of more than 140,000 synapses, both excitatory and inhibitory, within their individual domains, and form a syncytium that can propagate calcium waves to affect distant cells via release of “gliotransmitters” such as glutamate, ATP, or adenosine. Neuromodulators can affect signal-to-noise and frequency transmission within cortical circuits by effects on inhibition, allowing for the filtering of relevant vs. irrelevant stimuli. Moreover, synchronized “resting” and desynchronized “activated” brain states are gated by short bursts of high-frequency neuromodulatory activity, highlighting the need for neuromodulation that is robust, rapid, and far-reaching. As many neuromodulators are released in a volume manner where degradation/uptake and the confines of the complex CNS limit diffusion distance, we ask the question—are astrocytes responsible for rapidly extending neuromodulator actions to every synapse? Neuromodulators are known to influence transitions between brain states, leading to control over plasticity, responses to salient stimuli, wakefulness, and sleep. These rapid and wide-spread state transitions demand that neuromodulators can simultaneously influence large and diverse regions in a manner that should be impossible given the limitations of simple diffusion. Intriguingly, astrocytes are ideally situated to amplify/extend neuromodulator effects over large populations of synapses given that each astrocyte can: (1) ensheath a large number of synapses; (2) release gliotransmitters (glutamate/ATP/adenosine) known to affect inhibition; (3) regulate extracellular potassium that can affect excitability and excitation/inhibition balance; and (4) express receptors for all neuromodulators. In this review article, we explore the hypothesis that astrocytes extend and amplify neuromodulatory influences on neuronal networks via alterations in calcium dynamics, the release of gliotransmitters, and potassium homeostasis. Given that neuromodulatory networks are at the core of our sleep-wake cycle and behavioral states, and determine how we interact with our environment, this review article highlights the importance of basic astrocyte function in homeostasis, general cognition, and psychiatric disorders.
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spelling pubmed-75545222020-11-13 Astrocytes—The Ultimate Effectors of Long-Range Neuromodulatory Networks? Pacholko, Anthony G. Wotton, Caitlin A. Bekar, Lane K. Front Cell Neurosci Cellular Neuroscience It was long thought that astrocytes, given their lack of electrical signaling, were not involved in communication with neurons. However, we now know that one astrocyte on average maintains and regulates the extracellular neurotransmitter and potassium levels of more than 140,000 synapses, both excitatory and inhibitory, within their individual domains, and form a syncytium that can propagate calcium waves to affect distant cells via release of “gliotransmitters” such as glutamate, ATP, or adenosine. Neuromodulators can affect signal-to-noise and frequency transmission within cortical circuits by effects on inhibition, allowing for the filtering of relevant vs. irrelevant stimuli. Moreover, synchronized “resting” and desynchronized “activated” brain states are gated by short bursts of high-frequency neuromodulatory activity, highlighting the need for neuromodulation that is robust, rapid, and far-reaching. As many neuromodulators are released in a volume manner where degradation/uptake and the confines of the complex CNS limit diffusion distance, we ask the question—are astrocytes responsible for rapidly extending neuromodulator actions to every synapse? Neuromodulators are known to influence transitions between brain states, leading to control over plasticity, responses to salient stimuli, wakefulness, and sleep. These rapid and wide-spread state transitions demand that neuromodulators can simultaneously influence large and diverse regions in a manner that should be impossible given the limitations of simple diffusion. Intriguingly, astrocytes are ideally situated to amplify/extend neuromodulator effects over large populations of synapses given that each astrocyte can: (1) ensheath a large number of synapses; (2) release gliotransmitters (glutamate/ATP/adenosine) known to affect inhibition; (3) regulate extracellular potassium that can affect excitability and excitation/inhibition balance; and (4) express receptors for all neuromodulators. In this review article, we explore the hypothesis that astrocytes extend and amplify neuromodulatory influences on neuronal networks via alterations in calcium dynamics, the release of gliotransmitters, and potassium homeostasis. Given that neuromodulatory networks are at the core of our sleep-wake cycle and behavioral states, and determine how we interact with our environment, this review article highlights the importance of basic astrocyte function in homeostasis, general cognition, and psychiatric disorders. Frontiers Media S.A. 2020-09-29 /pmc/articles/PMC7554522/ /pubmed/33192327 http://dx.doi.org/10.3389/fncel.2020.581075 Text en Copyright © 2020 Pacholko, Wotton and Bekar. http://creativecommons.org/licenses/by/4.0/ 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.
spellingShingle Cellular Neuroscience
Pacholko, Anthony G.
Wotton, Caitlin A.
Bekar, Lane K.
Astrocytes—The Ultimate Effectors of Long-Range Neuromodulatory Networks?
title Astrocytes—The Ultimate Effectors of Long-Range Neuromodulatory Networks?
title_full Astrocytes—The Ultimate Effectors of Long-Range Neuromodulatory Networks?
title_fullStr Astrocytes—The Ultimate Effectors of Long-Range Neuromodulatory Networks?
title_full_unstemmed Astrocytes—The Ultimate Effectors of Long-Range Neuromodulatory Networks?
title_short Astrocytes—The Ultimate Effectors of Long-Range Neuromodulatory Networks?
title_sort astrocytes—the ultimate effectors of long-range neuromodulatory networks?
topic Cellular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554522/
https://www.ncbi.nlm.nih.gov/pubmed/33192327
http://dx.doi.org/10.3389/fncel.2020.581075
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