Cellular and network properties of the subiculum in the pilocarpine model of temporal lobe epilepsy.
The subiculum was recently shown to be crucially involved in the generation of interictal activity in human temporal lobe epilepsy. Using the pilocarpine model of epilepsy, this study examines the anatomical substrates for network hyperexcitability recorded in the subiculum. Regular- and burst-spiking subicular pyramidal cells were stained with fluorescence dyes and reconstructed to analyze seizure-induced alterations of the dendritic and axonal system. In control animals burst-spiking cells outnumbered regular-spiking cells by about two to one. Regular- and burst-spiking cells were characterized by extensive axonal branching and autapse-like contacts, suggesting a high intrinsic connectivity. In addition, subicular axons projecting to CA1 indicate a CA1-subiculum-CA1 circuit. In the subiculum of pilocarpine-treated rats we found an enhanced network excitability characterized by spontaneous rhythmic activity, polysynaptic responses, and all-or-none evoked bursts of action potentials. In pilocarpine-treated rats the subiculum showed cell loss of about 30%. The ratio of regular- and burst-spiking cells was practically inverse as compared to control preparations. A reduced arborization and spine density in the proximal part of the apical dendrites suggests a partial deafferentiation from CA1. In pilocarpine-treated rats no increased axonal outgrowth of pyramidal cells was observed. Hence, axonal sprouting of subicular pyramidal cells is not mandatory for the development of the pathological events. We suggest that pilocarpine-induced seizures cause an unmasking or strengthening of synaptic contacts within the recurrent subicular network.
Knopp
Andreas
A
Neuroscience Research Center of the Charité, Humboldt University of Berlin, D-10117 Berlin, Germany.
Kivi
Anatol
A
Wozny
Christian
C
Heinemann
Uwe
U
Behr
Joachim
J
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002452:Cell Count; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D049229:Dendritic Spines / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000473:pathology*; D005452:Fluoresceins; D018756:GABA Antagonists / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D066298:In Vitro Techniques; D008239:Lysine / Q000031:analogs & derivatives*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018721:Muscarinic Agonists; D009415:Nerve Net / Q000473:pathology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010862:Pilocarpine; D017966:Pyramidal Cells / Q000187:drug effects / Q000503:physiopathology* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D013194:Staining and Labeling / Q000379:methods
D005452:Fluoresceins; D018756:GABA Antagonists; D018721:Muscarinic Agonists; D010862:Pilocarpine; C013411:biocytin; D008239:Lysine; D001640:Bicuculline