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 Ca(2+) fluctuations that are heterogeneously distributed throughout different cellular microdomains. Changes in Ca(2+) dynamics represent a key mechanism for how astrocytes modulate neuronal activity. An unresolved issue is the origin and contribution of specific glial Ca(2+) 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(2+) signaling. Here we identify a role for ER store-operated Ca(2+) 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(2+) activity that varies based on their locale within the brain. Ca(2+) signaling in PG cells does not require extracellular Ca(2+) 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(2+) release from internal stores and its propagation between neighboring glial cells via gap junctions are essential for maintaining normal nervous system function.