title: Status Epilepticus Enhances Depotentiation after Fully Established LTP in an NMDAR-Dependent but GluN2B-Independent Manner.
abstract: N-Methyl-D-aspartate (NMDA) receptor-dependent long-term potentiation (LTP) can be reversed by low-frequency stimulation (LFS) referred to as depotentiation (DP). We previously found GluN2B upregulated in CA1 neurons from post-status epilepticus (post-SE) tissue associated with an enhanced LTP. Here, we tested whether LFS-induced DP is also altered in pathological GluN2B upregulation. Although LTP was enhanced in post-SE tissue, LTP was significantly reversed in this tissue, but not in controls. We next tested the effect of the GluN2B subunit-specific blocker Ro 25-6981 (1 μM) on LFS-DP. As expected, LFS had no effect on synaptic strength in the presence of the GluN2B blocker in control tissue. In marked contrast, LFS-DP was also attained in post-SE tissue indicating that GluN2B was obviously not involved in depotentiation. To test for NMDA receptor-dependence, we applied the NMDA receptor antagonist D-AP5 (50 μM) prior to LFS and observed that DP was abolished in both control and post-SE tissue confirming NMDA receptor involvement. These results indicate that control Schaffer collateral-CA1 synapses cannot be depotentiated after fully established LTP, but LFS was able to reverse LTP significantly in post-SE tissue. However, while LFS-DP clearly required NMDA receptor activation, GluN2B-containing NMDA receptors were not involved in this form of depotentiation.
authors.affiliation: Oscar Langendorff Institute of Physiology, University of Rostock, Gertrudenstraße 9, 18057 Rostock, Germany.
authors.forename: Xiati
authors.initials: X
authors.lastname: Guli
authors.affiliation: Oscar Langendorff Institute of Physiology, University of Rostock, Gertrudenstraße 9, 18057 Rostock, Germany; Center for Life Sciences, Nazarbayev University, 53 Kabanbay Batyr Avenue, Astana 010000, Kazakhstan.
authors.forename: Tursonjan
authors.initials: T
authors.lastname: Tokay
authors.affiliation: Oscar Langendorff Institute of Physiology, University of Rostock, Gertrudenstraße 9, 18057 Rostock, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Kirschstein
authors.affiliation: Oscar Langendorff Institute of Physiology, University of Rostock, Gertrudenstraße 9, 18057 Rostock, Germany.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Köhling
mesh_terms: D000818:Animals; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D017774:Long-Term Potentiation; D036881:Long-Term Synaptic Depression; D008297:Male; D010636:Phenols / Q000008:administration & dosage; D010862:Pilocarpine; D010880:Piperidines / Q000008:administration & dosage; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology*; D015854:Up-Regulation
chemical_list: C121001:NR2B NMDA receptor; D010636:Phenols; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981; D010862:Pilocarpine