Microdomain calcium oscillations in Drosophila glia regulate seizure susceptibility and require NCKX

Abstract

Glial cells exhibit spontaneous and activity-dependent fluctuations in intracellular Ca²+, yet it is unclear whether glial Ca²+ oscillations are required during neuronal signaling. Somatic glial Ca²+ waves are primarily mediated by the release of intracellular Ca²+ stores, and their relative importance in normal brain physiology has been disputed. Recently, near-membrane microdomain Ca²+ transients were identified in fine astrocytic processes and found to arise via an intracellular store- independent process. Here, we describe the identification of rapid, near-membrane Ca²+ oscillations in Drosophila cortex glia of the central nervous system. In a screen for temperature-sensitive conditional seizure mutants, we identified a glial-specific Na+/Ca²+, K+ exchanger (zydeco) that is required for microdomain Ca²+ oscillatory activity. We found that zydeco mutant animals exhibit increased susceptibility to seizures in response to several environmental stressors, and that zydeco is required acutely in cortex glia to regulate seizure susceptibility. We also found that glial expression of calmodulin is required for stress-induced seizures in zydeco mutants, suggesting a Ca²+/calmodulin-dependent glial signaling pathway is involved in acute glial-neuronal communication. These studies demonstrate that microdomain glial Ca²+ oscillations require NCKX-mediated plasma membrane Ca²+ flux, and are essential for normal neuronal excitability.