Glial Ca2+signaling links endocytosis to K+ buffering around neuronal somas to regulate excitability

• Main Authors: Weiss Sharabi, Shirley (Author), Melom, Jan Elizabeth (Author), Ormerod, Kiel G (Author), Zhang, Yao (Author), Littleton, J. Troy (Author)
• Other Authors: Picower Institute for Learning and Memory (Contributor), Massachusetts Institute of Technology. Department of Biology (Contributor), Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences (Contributor)
• Format: Article
• Language: English
• Published: eLife Sciences Publications, Ltd, 2020-05-27T15:39:39Z.
• Subjects: Article
• Online Access: Get fulltext

 Glial-neuronal signaling at synapses is widely studied, but how glia interact with neuronal somas to regulate their activity is unclear. Drosophila cortex glia are restricted to brain regions devoid of synapses, providing an opportunity to characterize interactions with neuronal somas. Mutations in the cortex glial NCKXzydecoelevate basal Ca2+, predisposing animals to seizure-like behavior. To determine how cortex glial Ca2+signaling controls neuronal excitability, we performed an in vivo modifier screen of the NCKXzydecoseizure phenotype. We show that elevation of glial Ca2+causes hyperactivation of calcineurin-dependent endocytosis and accumulation of early endosomes. Knockdown of sandman, a K2P channel, recapitulates NCKXzydecoseizures. Indeed, sandman expression on cortex glial membranes is substantially reduced in NCKXzydecomutants, indicating enhanced internalization of sandman predisposes animals to seizures. These data provide an unexpected link between glial Ca2+signaling and the well-known role of glia in K+buffering as a key mechanism for regulating neuronal excitability.