Sharp-wave ripples represent a prominent synchronous activity pattern in the mammalian hippocampus during sleep and immobility. GABAergic interneuronal types are silenced or fire during these events, but the mechanism of pyramidal cell (PC) participation remains elusive. We found opposite membrane polarization of deep (closer to stratum oriens) and superficial (closer to stratum radiatum) rat CA1 PCs during sharp-wave ripples. Using sharp and multi-site recordings in combination with neurochemical profiling, we observed a predominant inhibitory drive of deep calbindin (CB)-immunonegative PCs that contrasts with a prominent depolarization of superficial CB-immunopositive PCs. Biased contribution of perisomatic GABAergic inputs, together with suppression of CA2 PCs, may explain the selection of CA1 PCs during sharp-wave ripples. A deep-superficial gradient interacted with behavioral and spatial effects to determine cell participation during sleep and awake sharp-wave ripples in freely moving rats. Thus, the firing

Mechanisms involved in the transition to an epileptic seizure remain unclear. We studied this question in tissue slices from human subjects with mesial temporal lobe epilepsies. Ictal-like discharges were induced in the subiculum by increasing excitability together with an alkalinization or low Mg 2+ . During the transition, distinct pre-ictal discharges emerged concurrently with interictal events. Intracranial recordings from the mesial temporal cortex of epileptic subjects revealed similar discharges before seizures were restricted to seizure onset sites. In vitro, pre-ictal events spread faster, have a larger amplitude and a distinct initiation site than interictal discharges. They depend on glutamatergic mechanisms and are preceded by pyramidal cell firing, while interneuron firing precedes interictal events which depend on both glutamatergic and depolarizing GABAergic transmission. Once established, recurrence of these pre-ictal discharges triggers seizures. Thus the subiculum supports seizure generation and the transition to seizure involves a novel, emergent glutamatergic population activity.3