title: Dentate gyrus autonomous ictal activity in the status epilepticus rat model of epilepsy.
abstract: The dentate gyrus (DG) as part of the hippocampal formation is believed to serve as a gatekeeper with strong inhibitory properties against uncontrolled propagation of neuronal activity from the entorhinal cortex and neocortical structures. In temporal lobe epilepsy, the DG becomes hyperexcitable and loses its gate function, enabling propagation of ictal activity into downstream structures such as CA3 and CA1 areas. Furthermore, the DG, apart from facilitating propagation, may also be able to autonomously generate ictal activity, but this point has remained open so far. To tackle this question, we used intrinsic optical imaging in combination with electrophysiological recordings in brain slice preparations from rats in which status epilepticus had been induced electrically several weeks prior to measurements. Upon omission of Mg++from the artificial cerebrospinal fluid, in 15 out of 33 slices (45.4%) from 9 out of 13 epileptic animals (69.2%), spontaneous and autonomous ictal activity, mostly seizure-like events (SLE), was observed in the DG. This activity manifested independently from SLE generated in adjacent cortices and never occurred in slices from control animals. SLE generated in the DG differed from those with origin in the entorhinal or temporal cortex by longer latency to the first event after Mg++omission (p<0.001), a higher SLE frequency (p<0.05), higher amplitude (p<0.001) and a longer SLE duration (p<0.05). We conclude that in epilepsy, the DG, in addition to facilitated gating of activity from upstream structures, can serve as an independent generator of ictal activity.
authors.affiliation: Epilepsy-Center Berlin-Brandenburg, Department of Neurology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Weissinger
authors.affiliation: Epilepsy-Center Berlin-Brandenburg, Department of Neurology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. Electronic address: matthias.wawra@charite.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Wawra
authors.affiliation: Epilepsy-Center Berlin-Brandenburg, Department of Neurology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Pawel
authors.initials: P
authors.lastname: Fidzinski
authors.affiliation: Epilepsy-Center Berlin-Brandenburg, Department of Neurology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Elsner
authors.affiliation: Epilepsy-Center Berlin-Brandenburg, Department of Neurology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Meierkord
authors.affiliation: Epilepsy-Center Berlin-Brandenburg, Department of Neurology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Holtkamp
authors.affiliation: Epilepsy-Center Berlin-Brandenburg, Department of Neurology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Buchheim
mesh_terms: D000818:Animals; D018891:Dentate Gyrus / Q000503:physiopathology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D018728:Entorhinal Cortex / Q000503:physiopathology; D019706:Excitatory Postsynaptic Potentials; D008275:Magnesium Deficiency; D008297:Male; D008839:Microelectrodes; D061848:Optical Imaging; D017208:Rats, Wistar; D013226:Status Epilepticus / Q000503:physiopathology*; D046509:Tissue Culture Techniques
keywords: Hippocampus; Intrinsic optical signal; Low Mg(++) model; Slice electrophysiology; Sustained stimulation