Glial ER and GAP junction mediated Ca 2+ waves are crucial to maintain normal brain excitability

Astrocytes play key roles in regulating multiple aspects of neuronal function from invertebrates to humans and display Ca2+ fluctuations that are heterogeneously distributed throughout different cellular microdomains. Changes in Ca2+ dynamics represent a key mechanism for how astrocytes modulate neu...

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Main Authors: Weiss, Shirley, Clamon, Lauren C, Manoim, Julia E, Ormerod, Kiel G, Parnas, Moshe, Littleton, J Troy
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:English
Published: Wiley 2022
Online Access:https://hdl.handle.net/1721.1/146892
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author Weiss, Shirley
Clamon, Lauren C
Manoim, Julia E
Ormerod, Kiel G
Parnas, Moshe
Littleton, J Troy
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Weiss, Shirley
Clamon, Lauren C
Manoim, Julia E
Ormerod, Kiel G
Parnas, Moshe
Littleton, J Troy
author_sort Weiss, Shirley
collection MIT
description Astrocytes play key roles in regulating multiple aspects of neuronal function from invertebrates to humans and display Ca2+ fluctuations that are heterogeneously distributed throughout different cellular microdomains. Changes in Ca2+ dynamics represent a key mechanism for how astrocytes modulate neuronal activity. An unresolved issue is the origin and contribution of specific glial Ca2+ signaling components at distinct astrocytic domains to neuronal physiology and brain function. The Drosophila model system offers a simple nervous system that is highly amenable to cell-specific genetic manipulations to characterize the role of glial Ca2+ signaling. Here we identify a role for ER store-operated Ca2+ entry (SOCE) pathway in perineurial glia (PG), a glial population that contributes to the Drosophila blood-brain barrier. We show that PG cells display diverse Ca2+ activity that varies based on their locale within the brain. Ca2+ signaling in PG cells does not require extracellular Ca2+ and is blocked by inhibition of SOCE, Ryanodine receptors, or gap junctions. Disruption of these components triggers stimuli-induced seizure-like episodes. These findings indicate that Ca2+ release from internal stores and its propagation between neighboring glial cells via gap junctions are essential for maintaining normal nervous system function.
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spelling mit-1721.1/1468922022-12-16T03:27:34Z Glial ER and GAP junction mediated Ca 2+ waves are crucial to maintain normal brain excitability Weiss, Shirley Clamon, Lauren C Manoim, Julia E Ormerod, Kiel G Parnas, Moshe Littleton, J Troy Massachusetts Institute of Technology. Department of Biology Astrocytes play key roles in regulating multiple aspects of neuronal function from invertebrates to humans and display Ca2+ fluctuations that are heterogeneously distributed throughout different cellular microdomains. Changes in Ca2+ dynamics represent a key mechanism for how astrocytes modulate neuronal activity. An unresolved issue is the origin and contribution of specific glial Ca2+ signaling components at distinct astrocytic domains to neuronal physiology and brain function. The Drosophila model system offers a simple nervous system that is highly amenable to cell-specific genetic manipulations to characterize the role of glial Ca2+ signaling. Here we identify a role for ER store-operated Ca2+ entry (SOCE) pathway in perineurial glia (PG), a glial population that contributes to the Drosophila blood-brain barrier. We show that PG cells display diverse Ca2+ activity that varies based on their locale within the brain. Ca2+ signaling in PG cells does not require extracellular Ca2+ and is blocked by inhibition of SOCE, Ryanodine receptors, or gap junctions. Disruption of these components triggers stimuli-induced seizure-like episodes. These findings indicate that Ca2+ release from internal stores and its propagation between neighboring glial cells via gap junctions are essential for maintaining normal nervous system function. 2022-12-15T18:54:59Z 2022-12-15T18:54:59Z 2022 2022-12-15T18:37:59Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/146892 Weiss, Shirley, Clamon, Lauren C, Manoim, Julia E, Ormerod, Kiel G, Parnas, Moshe et al. 2022. "Glial ER and GAP junction mediated Ca 2+ waves are crucial to maintain normal brain excitability." Glia, 70 (1). en 10.1002/GLIA.24092 Glia Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley PMC
spellingShingle Weiss, Shirley
Clamon, Lauren C
Manoim, Julia E
Ormerod, Kiel G
Parnas, Moshe
Littleton, J Troy
Glial ER and GAP junction mediated Ca 2+ waves are crucial to maintain normal brain excitability
title Glial ER and GAP junction mediated Ca 2+ waves are crucial to maintain normal brain excitability
title_full Glial ER and GAP junction mediated Ca 2+ waves are crucial to maintain normal brain excitability
title_fullStr Glial ER and GAP junction mediated Ca 2+ waves are crucial to maintain normal brain excitability
title_full_unstemmed Glial ER and GAP junction mediated Ca 2+ waves are crucial to maintain normal brain excitability
title_short Glial ER and GAP junction mediated Ca 2+ waves are crucial to maintain normal brain excitability
title_sort glial er and gap junction mediated ca 2 waves are crucial to maintain normal brain excitability
url https://hdl.handle.net/1721.1/146892
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