Two electrophysiologically distinct types of granule cells in epileptic human hippocampus

We investigated the electrophysiology of morphologically identified human g ranule cells with conventional current-clamp recordings. Slices were prepar ed from 14 human epileptic sclerotic hippocampi. Granule cells appeared to have a diverse electrophysiology. Each cell was distinguished by the shape of the afterhyperpolarization following single action potentials. Two types could be discerned: type I afterhyperpolarizations were monophasic and bri ef(typically 10-40 ms), whilst type Il afterhyperpolarizations were biphasi c and long (typically 50-100 ms). The two types also differed in their repe titive firing behaviour and action potential morphology: type I cells had s ignificantly weaker spike frequency adaptation, lower action potential ampl itude and smaller action potential upstroke/downstroke ratio. Thus, the fir ing pattern of type I cells resembled that of rodent dentate interneurons. In contrast, the corresponding parameters of type II cells were comparable to rodent dentate granule cells. Despite the distinct firing patterns, memb rane properties were not different. The two types of cells also differed in their synaptic responses to stimulation of the perforant path. At strong s uprathreshold stimulation intensity, type I cells always generated multiple action potentials, whereas type II cells usually spiked once only. Slow in hibitory postsynaptic potentials were not detected in type I neurons, but w ere easily identified in type II neurons. Extracellular recordings of perfo rant path-evoked field potentials in the cell layer confirmed that the majo rity of granule cells showed multiple discharges even when we recorded simu ltaneously from a type II cell that generated one action potential only. Th e morphology of both types of cells was characteristic of what has been des cribed for primate dentate granule cells. Based on comparisons with previous studies on rodent and human granule cell s, we tentatively hypothesize that: (i) the majority of granule cells from sclerotic hippocampus display an hyperexcitable epileptogenic electrophysio logy; (ii) there is a subset of granule cells whose electrophysiology is pr eserved and is more comparable to granule cells from non-epileptic hippocam pus. (C) 1999 IBRO. Published by Elsevier Science Ltd.