Re-entrant activity in a presubiculum–subiculum circuit generates epileptiform activity in vitro

The retrohippocampal cortices form the transition between neocortex and the hippocampus. Area CA3 of the hippocampus and the entorhinal cortex (EC) of the retrohippocampal region are established as brain regions that generate epileptiform activity. Interictal activity generated in EC consists of a primary population burst followed by multiple afterdischarges. The presubiculum is similar to EC in its six-layered structure, but lacks a columnar circuitry that the EC possesses. Isolated presubicular tissue cannot generate afterdischarges and isolated subicular tissue generates no spontaneous activity under some conditions. We report epileptiform activity in combined presubiculum-subiculum slices that consists of synchronous population bursts and multiple afterdischarges. Intracellular and field potential recordings reveal two re-entrant paths for interaction of presubicular and subicular neurons. We demonstrate a deep presubicular input to subiculum and separate return paths from subicular bursting neurons onto deep and superficial layer pre-/parasubicular neurons. Recordings from subicular cell apical dendrites showed repetitive burst firing during sustained depolarizing current injection. We conclude that re-entrant activity in a presubiculum-subiculum circuit generates epileptiform activity in both regions. Presubicular inputs to subiculum depolarize apical dendrites which can then burst repetitively. These bursts are transmitted back to the presubiculum. We suggest that iterations on this circuit act to prolong the dendritic depolarization of subicular bursting neurons and to entrain the activity across subicular cells resulting in multiple afterdischarges.