Glial ER and GAP junction mediated Ca2+ waves are crucial to maintain normal brain excitability

Shirley Weiss*, Lauren C. Clamon, Julia E. Manoim, Kiel G. Ormerod, Moshe Parnas, J. Troy Littleton

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)123-144
Number of pages22
JournalGLIA
Volume70
Issue number1
DOIs
StatePublished - Jan 2022

Funding

FundersFunder number
Israeli Ministry for Science and TechnologyNIHP40OD018537
National Institutes of HealthNS40296
National Institute of Mental HealthR01MH104536
Deutsche Forschungsgemeinschaft408264519
Israel Science Foundation343/18
Ministry of Science and Technology, Israel

    Keywords

    • Ca waves
    • Drosophila
    • perineurial glia
    • seizures
    • store-operated Ca entry

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