Figure 8.

Restoration of ECS volume in Has3^−/− slices blocks spontaneous epileptiform activity, whereas reduction of ECS volume in WT slices mimics Has3^−/− phenotype. A, In Has3^−/− slices, hypertonic conditions (400 mosmol/kg) were used to shift water from the intra- to the extracellular compartment and increase ECS volume fraction α. This manipulation reversibly blocked spontaneous epileptiform activity in the CA1 hippocampus. B, In WT slices, hypotonic conditions (200 mosmol/kg) were used to shift water from the extracellular to the intracellular compartment and decrease the ECS volume fraction. This manipulation induced spontaneous epileptiform activity in the CA1 hippocampus, which was blocked upon return to normo-osmotic ACSF. C, Epileptiform activity induced in WT brain slices was reversibly blocked by NBQX. This NBQX sensitivity was also observed in Has3^−/− slices (Fig. 3B). Field potential recordings were made with electrode placed in the CA1 stratum pyramidale.