What causes seizure in focal epilepsy?

Publishing next week in the online, open access journal PLoS Biology, a new study reveals that early activation of astroglia, the main population of glial cells in the brain, by hyperactive neurons is one of the crucial events that predisposes neurons nearby to the generation of an epileptic discharge.

By monitoring the activity of neurons and astroglia by simultaneous single or dual patch-clamp recordings, field potential recordings, and Ca2+ signal imaging in different experimental models of epilepsy, Giorgio Carmignoto and colleagues at the National Research Council, Italy, found that an episode of hyperactivity in a restricted group of neurons massively activates nearby astrocytes. Activated astrocytes, in turn, signal back to neurons and potentiate hypersynchronized neuronal activity. In conditions of enhanced excitability, this astrocyte feedback signal drives neurons towards the seizure-like discharge threshold. Accordingly, selective inhibition or stimulation of astrocyte Ca2+ signalling reduced or enhanced, respectively, seizure discharge generation. Epileptic discharge, in turn, triggers a second activation of astrocytes that may favour seizure propagation.

In summary, this study reveals that a recurrent excitatory loop between neurons and astrocytes developing at restricted brain sites promotes and sustains epileptic seizures. This neuron-astrocyte interaction may represent a novel target for the development of effective therapeutic strategies to control epilepsy and target drug-resistant forms of the condition.

This work was supported by grants from the European Community 7th Framework Program (NeuroGlia, HEALTH-F2-2007-202167), Telethon Italy (GGP07278), and CARIPARO foundation. MGG was also supported by the MEC (Spain).