Light and temperature sensitive seizures are regulated by spatially distinct cortex glial populations in the central...

Epilepsy is a brain disorder, characterized by recurrent seizures due to abnormal neuronal activity originating from a population of cortical neurons. It is known that seizures are often associated with abnormal glial cell function at the seizure focus. Recent studies have shown that each glial type such as astrocytes display significant degree of heterogeneity in their development, molecular signatures, and function depending on the brain region in which they are located. It is unknown if such heterogeneity differentially influence/cause seizures. Previous studies in Drosophila have shown that aberrant cortex glial function led to light inducible seizures in Ceramide phosphoethanolamine synthase (cpes) and temperature inducible seizures in zyd mutants. Here, we have optimized Gal4/Split-Gal4/Gal80/LexA drivers to specifically express a gene of interest throughout development in cortex glial subpopulations in different parts of the brain including optic lobe (OL), central brain (CB) and ventral nerve cord (VNC). Using these tools, we performed brain region specific cortex glial rescue experiments in cpes and zyd mutants. We found that OL and CB, but not VNC specific cortex glial expression of UAS CPES, were able to significantly suppress light inducible seizures in cpes mutants. In contrast, VNC but not OL or CB specific cortex glial expression of UAS Zyd suppressed temperature sensitive seizures. Further, in a third model, expression and activation of transient receptor potential (dTrpA1) just in the VNC specific cortex glia was sufficient to induce temperature sensitive seizures in wild type flies. Our findings suggest that regionally specialized cortex glial subtypes differentially regulate seizure susceptibility in seizure models.