Local Efficacy of Glutamate Uptake Decreases with Synapse Size
Summary: Synaptically released glutamate is largely cleared by glutamate transporters localized on perisynaptic astrocyte processes. Therefore, the substantial variability of astrocyte coverage of individual hippocampal synapses implies that the efficacy of local glutamate uptake and thus the spatia...
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Elsevier
2020-09-01
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Series: | Cell Reports |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124720311712 |
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author | Michel K. Herde Kirsten Bohmbach Cátia Domingos Natascha Vana Joanna A. Komorowska-Müller Stefan Passlick Inna Schwarz Colin J. Jackson Dirk Dietrich Martin K. Schwarz Christian Henneberger |
author_facet | Michel K. Herde Kirsten Bohmbach Cátia Domingos Natascha Vana Joanna A. Komorowska-Müller Stefan Passlick Inna Schwarz Colin J. Jackson Dirk Dietrich Martin K. Schwarz Christian Henneberger |
author_sort | Michel K. Herde |
collection | DOAJ |
description | Summary: Synaptically released glutamate is largely cleared by glutamate transporters localized on perisynaptic astrocyte processes. Therefore, the substantial variability of astrocyte coverage of individual hippocampal synapses implies that the efficacy of local glutamate uptake and thus the spatial fidelity of synaptic transmission is synapse dependent. By visualization of sub-diffraction-limit perisynaptic astrocytic processes and adjacent postsynaptic spines, we show that, relative to their size, small spines display a stronger coverage by astroglial transporters than bigger neighboring spines. Similarly, glutamate transients evoked by synaptic stimulation are more sensitive to pharmacological inhibition of glutamate uptake at smaller spines, whose high-affinity N-methyl-D-aspartate receptors (NMDARs) are better shielded from remotely released glutamate. At small spines, glutamate-induced and NMDAR-dependent Ca2+ entry is also more strongly increased by uptake inhibition. These findings indicate that spine size inversely correlates with the efficacy of local glutamate uptake and thereby likely determines the probability of synaptic crosstalk. |
first_indexed | 2024-12-19T09:59:45Z |
format | Article |
id | doaj.art-db94c07843ce4150be52cf0a045b7c15 |
institution | Directory Open Access Journal |
issn | 2211-1247 |
language | English |
last_indexed | 2024-12-19T09:59:45Z |
publishDate | 2020-09-01 |
publisher | Elsevier |
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series | Cell Reports |
spelling | doaj.art-db94c07843ce4150be52cf0a045b7c152022-12-21T20:26:41ZengElsevierCell Reports2211-12472020-09-013212108182Local Efficacy of Glutamate Uptake Decreases with Synapse SizeMichel K. Herde0Kirsten Bohmbach1Cátia Domingos2Natascha Vana3Joanna A. Komorowska-Müller4Stefan Passlick5Inna Schwarz6Colin J. Jackson7Dirk Dietrich8Martin K. Schwarz9Christian Henneberger10Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, GermanyInstitute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, GermanyInstitute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, GermanyDepartment for Neurosurgery, University Hospital Bonn, Bonn, GermanyInstitute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, GermanyInstitute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, GermanyInstitute of Epileptology, Medical Faculty, University of Bonn, Bonn, GermanyResearch School of Chemistry, Australian National University, Canberra, AustraliaDepartment for Neurosurgery, University Hospital Bonn, Bonn, GermanyInstitute of Epileptology, Medical Faculty, University of Bonn, Bonn, GermanyInstitute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, Germany; Institute of Neurology, University College London, London, UK; German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany; Corresponding authorSummary: Synaptically released glutamate is largely cleared by glutamate transporters localized on perisynaptic astrocyte processes. Therefore, the substantial variability of astrocyte coverage of individual hippocampal synapses implies that the efficacy of local glutamate uptake and thus the spatial fidelity of synaptic transmission is synapse dependent. By visualization of sub-diffraction-limit perisynaptic astrocytic processes and adjacent postsynaptic spines, we show that, relative to their size, small spines display a stronger coverage by astroglial transporters than bigger neighboring spines. Similarly, glutamate transients evoked by synaptic stimulation are more sensitive to pharmacological inhibition of glutamate uptake at smaller spines, whose high-affinity N-methyl-D-aspartate receptors (NMDARs) are better shielded from remotely released glutamate. At small spines, glutamate-induced and NMDAR-dependent Ca2+ entry is also more strongly increased by uptake inhibition. These findings indicate that spine size inversely correlates with the efficacy of local glutamate uptake and thereby likely determines the probability of synaptic crosstalk.http://www.sciencedirect.com/science/article/pii/S2211124720311712glutamate uptakeastrocyteshippocampusastrocyte morphologyspine morphologymultiphoton imaging |
spellingShingle | Michel K. Herde Kirsten Bohmbach Cátia Domingos Natascha Vana Joanna A. Komorowska-Müller Stefan Passlick Inna Schwarz Colin J. Jackson Dirk Dietrich Martin K. Schwarz Christian Henneberger Local Efficacy of Glutamate Uptake Decreases with Synapse Size Cell Reports glutamate uptake astrocytes hippocampus astrocyte morphology spine morphology multiphoton imaging |
title | Local Efficacy of Glutamate Uptake Decreases with Synapse Size |
title_full | Local Efficacy of Glutamate Uptake Decreases with Synapse Size |
title_fullStr | Local Efficacy of Glutamate Uptake Decreases with Synapse Size |
title_full_unstemmed | Local Efficacy of Glutamate Uptake Decreases with Synapse Size |
title_short | Local Efficacy of Glutamate Uptake Decreases with Synapse Size |
title_sort | local efficacy of glutamate uptake decreases with synapse size |
topic | glutamate uptake astrocytes hippocampus astrocyte morphology spine morphology multiphoton imaging |
url | http://www.sciencedirect.com/science/article/pii/S2211124720311712 |
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