Transient Switching of NMDA-Dependent Long-Term Synaptic Potentiation in CA3-CA1 Hippocampal Synapses to mGluR1-Dependent Potentiation After Pentylenetetrazole-Induced Acute Seizures in Young Rats
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The mechanisms of impairment in long-term potentiation after status epilepticus (SE) remain unclear. We investigated the properties of LTP induced by theta-burst stimulation in hippocampal slices of rats 3 h and 1, 3, and 7 days after SE. Seizures were induced in 3-week old rats by a single injection of pentylenetetrazole (PTZ). Only animals with generalized seizures lasting more than 30 min were included in the experiments. The results revealed that LTP was strongly attenuated in the CA1 hippocampal area after PTZ-induced SE as compared with that in control animals. Saturation of synaptic responses following epileptic activity does not explain weakening of LTP because neither the quantal size of the excitatory responses nor the slopes of the input–output curves for field excitatory postsynaptic potentials changed in the post-SE rats. After PTZ-induced SE, NMDA-dependent LTP was suppressed, and LTP transiently switched to the mGluR1-dependent form. This finding does not appear to have been reported previously in the literature. An antagonist of NMDA receptors, d-2-amino-5-phosphonovalerate, did not block LTP induction in 3-h and 1-day post-SE slices. An antagonist of mGluR1, FTIDS, completely prevented LTP in 1-day post-SE slices; whereas it did not affect LTP induction in control and post-SE slices at the other studied times. mGluR1-dependent LTP was postsynaptically expressed and did not require NMDA receptor activation. Recovery of NMDA-dependent LTP occurred 7 day after SE. Transient switching between NMDA-dependent LTP and mGluR1-dependent LTP could play a role in the pathogenesis of acquired epilepsy.
KeywordsLong-term potentiation Group I mGlu receptor mGluR-dependent plasticity NMDA receptor Epilepsy Animal model
TP, OZ, and AZ designed the study. TP, JE, AT, SK, and OZ performed experiments and analyzed data. TP, JE, AT, OZ, SK, and AZ interpreted data for the work. TP, JE, OZ, and AZ wrote the manuscript. TP, EJ, AT, OZ, SK, and AZ approved the final version.
This study was funded by the Russian Science Foundation (project 16-15-10202) and the experiments shown in Fig. 4 by the Russian Foundation for Basic Research (project 17-00-00408).
Compliance with Ethical Standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and institutional guidelines for the care and use of animals were followed.
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