Glial ER and GAP junction mediated Ca 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 Ca fluctuations that are heterogeneously distributed throughout different cellular microdomains. Changes in Ca dynamics represent a key mechanism for how astrocytes modulate neuronal activity. An unresolved issue is the origin and contribution of specific glial Ca 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 Ca signaling. Here we identify a role for ER store-operated Ca 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 Ca activity that varies based on their locale within the brain. Ca signaling in PG cells does not require extracellular Ca 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 Ca release from internal stores and its propagation between neighboring glial cells via gap junctions are essential for maintaining normal nervous system function.