Presubiculum stimulation in vivo evokes distinct oscillations in superficial and deep entorhinal cortex layers in chronic epileptic rats

The characteristic cell loss in layer III of the medial entorhinal area (MEA-III) in human mesial temporal lobe epilepsy is reproduced in the rat kainate model of the disease. To understand how this cell loss affects the functional properties of the MEA, we investigated whether projections from the presubiculum (prS), providing a main input to the MEA-III, are altered in this epileptic rat model. Injections of an anterograde tracer in the prS revealed bilateral projection fibers mainly to the MEA- III in both control and chronic epileptic rats. We further examined the prS-MEA circuitry using a 16-channel electrode probe covering the MEA in anesthetized control and chronic epileptic rats. With a second 16-channel probe, we recorded signals in the hippocampus. Current source density analysis indicated that, after prS double-pulse stimulation, afterdischarges in the form of oscillations (20-45 Hz) occurred that were confined to the superficial layers of the MEA in all epileptic rats displaying MEA-III neuronal loss. Slower oscillations ( theta range) were occasionally observed in the deep MEA layers and the dentate gyrus. This kind of oscillation was never observed in control rats. We conclude that dynamical changes occur in an extensive network within the temporal lobe in epileptic rats, manifested as different kinds of oscillations, the characteristics of which depend on local properties of particular subareas. These findings emphasize the significance of the entorhinal cortex in temporal lobe epilepsy and suggest that the superficial cell layers could play an important role in distributing oscillatory activity.