Astrocytes get in the act in epilepsy

Abstract

Neurons in the brain of individuals with focal epilepsy exhibit sustained discharges, called paroxysmal depolarization shifts. Unexpected new evidence indicates that glutamate release from glia can generate these events, and may serve to synchronize the activity of neurons.

Figure 1.

Glutamate released from astrocytes generates a paroxysmal depolarization shift (PDS), the elemental electrophysiological event in focal epilepsy. Astrocytes form a multicellular functional syncytium as a result of gap-junctional coupling between processes of the same and neighboring astrocytes. Calcium waves within the astrocytic syncytium induce release of glutamate from astrocytes. Glutamate diffuses to dendritic AMPA and NMDA receptors of nearby neurons, inducing a depolarizing (excitatory) response. The glutamate release from astrocytes could occur as a result of calcium-dependent exocytosis, or diffusion through ionotropic purinergic receptors or gap junction hemichannels. In an experimental epilepsy model, the glutamate release is sufficient to elicit a PDS-like membrane depolarization that evokes a train of action potentials and is followed by membrane hyperpolarization. Recording from an astrocyte reveals a slow depolarization that coincides with the PDS but is more prolonged in duration. An extracellular electrode records a negative-going field potential (similar to an electroencepalographic ‘spike’) representing summated dendritic inward currents of the synchronously occurring PDSs in many neurons in the aggregate. Artist: Katie Ris.