Physiological changes in chronic epileptic rats are prominent in superficial layers of the medial entorhinal area

Purpose: We investigated whether the functional network properties of the medial entorhinal area (MEA) of the entorhinal cortex were altered in a rat model of chronic epilepsy that is characterized by extensive cell loss in MEA layer III. Methods: Responses were evoked in the entorhinal cortex by electrical stimulation of the subiculum in anesthetized chronic epileptic rats, 2-4 months after status epilepticus, induced by systemic kainate (KA) injections. Laminar field potentials were measured using a 16-channel silicon probe that covered all six layers of the MEA; an estimate of the local transmembrane currents was made using current source density analysis. Results: Double-pulse stimulation of the subiculum evoked responses in deep and superficial layers of the MEA in control and KA rats. A current sink in layer I and at the border of layer I and II that was induced by antidromic activation of MEA-II, was much more prominent in KA rats with extensive neuronal loss in MEA-III than in control rats or KA rats with minor MEA-III loss.Furthermore, KA rats that displayed MEA-III loss presented a series of oscillations induced by subicular stimulation in the Ply frequency range (20-100 Hz), which were confined to superficial layers of MEA. These oscillations were never observed in control rats or KA rats with minor MEA-III loss. Conclusions: These results indicate that the observed alterations in the superficial MEA responses to subiculum stimulation and the occurrence of beta/gamma-oscillations are related phenomena, which are a consequence of altered and impaired inhibition within these MEA layers in chronic epileptic rats. Key Words: Plasticity-Epileptogenesis-Parahippocam pal region-Subiculum stimulation-Current source density-Field potentials. Abbreviations: CA cornu ammonis-CSD current source density-EC entorhinal cortex-GC granule cells-KA kainic acid-MEA medial entorhinal area-MTLE mesial temporal lobe epilepsy-PrS presubiculum-SE status epitepticus-Sub subiculum-wm white matter.