Rapid astrocyte morphology changes support epileptic activity
1 Institute of Cellular Neurosciences, University of Bonn Medical School, Bonn, Germany
Astrocytes actively contribute to the functioning of neuronal networks by closely contacting to thousands of neurons. Their dysfunction and long-term morphology changes have been implicated in numerous diseases including epilepsy. How rapid astrocyte morphology is altered by the onset of epileptiform activity and to what degree this contributes to aberrant network activity is largely unknown. Combining established protocols of hippocampal epileptogenesis, electrophysiology and two-photon excitation fluorescence microscopy allowed us to monitor astrocyte morphology changes during the induction of epileptiform activity in acute hippocampal slices. Analysis revealed that small and medium-sized astrocyte processes shrink acutely within minutes after the onset of epileptiform discharges in the CA1 region. Importantly, these astrocyte morphology changes outlasted the induction of epileptiform activity, persisted after pharmacological termination of epileptic activity by TTX and were sensitive to inhibition of Rho-associated protein kinase (ROCK). Interestingly, ROCK inhibition also reduced epileptiform activity, indicating that rapid astrocyte morphology changes support epileptic activity. We observed that intracellular diffusion in astrocytes and diffusion between astrocytes via gap junctions were significantly decreased in parallel to morphology changes. Thus, astrocytes respond to epileptic activity with morphology changes on a time scale of minutes, which reduces intra- and intercellular diffusion in the astrocyte network and supports further epileptic activity. Finally, we investigated the mechanism(s) linking acute astrocyte morphology changes and the maintenance of epileptiform activity. However, inhibitory input on CA1 pyramidal neurons, extracellular space structure and extracellular glutamate and potassium clearance seem to be unaffected by the induction of epileptiform acitivity.