title: Two electrophysiologically distinct types of granule cells in epileptic human hippocampus.
abstract: We investigated the electrophysiology of morphologically identified human granule cells with conventional current-clamp recordings. Slices were prepared 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 brief (typically 10-40 ms), whilst type II afterhyperpolarizations were biphasic and long (typically 50-100 ms). The two types also differed in their repetitive firing behaviour and action potential morphology: type I cells had significantly weaker spike frequency adaptation, lower action potential amplitude and smaller action potential upstroke/downstroke ratio. Thus, the firing 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, membrane properties were not different. The two types of cells also differed in their synaptic responses to stimulation of the perforant path. At strong suprathreshold stimulation intensity, type I cells always generated multiple action potentials, whereas type II cells usually spiked once only. Slow inhibitory postsynaptic potentials were not detected in type I neurons, but were easily identified in type II neurons. Extracellular recordings of perforant path-evoked field potentials in the cell layer confirmed that the majority of granule cells showed multiple discharges even when we recorded simultaneously from a type II cell that generated one action potential only. The morphology of both types of cells was characteristic of what has been described for primate dentate granule cells. Based on comparisons with previous studies on rodent and human granule cells, we tentatively hypothesize that: (i) the majority of granule cells from sclerotic hippocampus display an hyperexcitable epileptogenic electrophysiology; (ii) there is a subset of granule cells whose electrophysiology is preserved and is more comparable to granule cells from non-epileptic hippocampus.
authors.affiliation: Klinik für Neurochirurgie, Universität Bonn, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Dietrich
authors.forename: H
authors.initials: H
authors.lastname: Clusmann
authors.forename: T
authors.initials: T
authors.lastname: Kral
authors.forename: C
authors.initials: C
authors.lastname: Steinhäuser
authors.forename: I
authors.initials: I
authors.lastname: Blümcke
authors.forename: U
authors.initials: U
authors.lastname: Heinemann
authors.forename: J
authors.initials: J
authors.lastname: Schramm
mesh_terms: D000328:Adult; D004558:Electric Stimulation; D004594:Electrophysiology; D004827:Epilepsy / Q000473:pathology* / Q000503:physiopathology*; D006624:Hippocampus / Q000473:pathology* / Q000503:physiopathology*; D006801:Humans; D009474:Neurons / Q000145:classification* / Q000502:physiology*; D019580:Perforant Pathway / Q000503:physiopathology; D013194:Staining and Labeling; D013569:Synapses / Q000502:physiology