Tight Coupling of Astrocyte pH Dynamics to Epileptiform Activity Revealed by Genetically Encoded pH Sensors

Objective: The brain consists of two types of cells, neurons and glia. Considerable research in epilepsy has focused on neurons, but the role of glia in seizure disorders is just beginning to be understood. Astrocytes are star-shaped glial cells that are extremely responsive to changes in the environment, and are important for supplying the brain with nutrients, forming the blood-brain barrier and for repairing the brain after injury.

pH is a measure of how acidic or alkaline (basic) something is, and pH changes have been noticed during seizure activity. Specifically, pH changes in neurons during seizures have been examined, but glial pH during a seizure has not been explored in detail. Hence, the scientists wanted to examine changes in astrocytic pH during a seizure and the timeframe in which these pH changes occur. This study is unique because the authors used genetically-coded pH sensitive proteins to observe pH changes in real time while measuring the electrical activity during a seizure. Seizures were elicited in tissue obtained from rodents. The hope is that by tracking pH changes, we can study their contribution to seizures and potentially find therapies to limit these changes and stop seizures.

Results: Earlier results have shown that pH in neurons during a seizure tends towards acidification. The mechanisms that regulate pH in astrocytes are different from those in neurons, and the authors found that astrocytes become alkaline during seizure-like events. The change in pH in astrocytes was much more rapid and more tightly coupled to network dynamics as compared to neuronal pH changes.

Interpretation: This study highlights notable differences between neurons and astrocytes in the way they regulate pH and possibly seizures. Since astrocytes seem to be more responsive than neurons to changes in local environment, targeting them could provide novel therapies for seizures and epilepsies.

Summary for specialists