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
- 143 Downloads
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.
- Amakhin DV, Malkin SL, Ergina JL, Kryukov KA, Veniaminova EA, Zubareva OE, Zaitsev AV (2017) Alterations in properties of glutamatergic transmission in the temporal cortex and hippocampus following pilocarpine-induced acute seizures in wistar rats. Front Cell Neurosci 11:264 https://doi.org/10.3389/fncel.2017.00264 CrossRefGoogle Scholar
- Aniol VA, Ivanova-Dyatlova AY, Keren O, Guekht AB, Sarne Y, Gulyaeva NV (2013) A single pentylenetetrazole-induced clonic-tonic seizure episode is accompanied by a slowly developing cognitive decline in rats. Epilepsy Behav 26:196–202. https://doi.org/10.1016/j.yebeh.2012.12.006 CrossRefGoogle Scholar
- Assaf F, Fishbein M, Gafni M, Keren O, Sarne Y (2011) Pre- and post-conditioning treatment with an ultra-low dose of Delta9-tetrahydrocannabinol (THC) protects against pentylenetetrazole (PTZ)-induced cognitive damage Behav. Brain Res 220:194–201. https://doi.org/10.1016/j.bbr.2011.02.005 Google Scholar
- Bikbaev A, Manahan-Vaughan D (2017) Metabotropic glutamate receptor, mGlu5, regulates hippocampal synaptic plasticity and is required for tetanisation-triggered changes in theta and gamma oscillations. Neuropharmacology 115:20–29. https://doi.org/10.1016/j.neuropharm.2016.06.004 CrossRefGoogle Scholar
- Bortolotto ZA, Collett VJ, Conquet F, Jia Z, van der Putten H, Collingridge GL (2005) The regulation of hippocampal LTP by the molecular switch, a form of metaplasticity, requires mGlu5 receptors. Neuropharmacology 49(Suppl 1):13–25 https://doi.org/10.1016/j.neuropharm.2005.05.020 CrossRefGoogle Scholar
- Cunha AO, de Oliveira JA, Almeida SS, Garcia-Cairasco N, Leao RM (2015) Inhibition of long-term potentiation in the schaffer-CA1 pathway by repetitive high-intensity sound stimulation. Neuroscience 310:114–127. https://doi.org/10.1016/j.neuroscience.2015.09.040 CrossRefGoogle Scholar
- Halgren E et al (1991) Memory dysfunction in epilepsy patients as a derangement of normal physiology. Adv Neurol 55:385–410Google Scholar
- Postnikova TY, Zubareva OE, Kovalenko AA, Kim KK, Magazanik LG, Zaitsev AV (2017) Status epilepticus impairs synaptic plasticity in rat hippocampus and is followed by changes in expression of NMDA receptors. Biochemistry (Moscow) 82:282–290. https://doi.org/10.1134/s0006297917030063 CrossRefGoogle Scholar
- Remigio GJ, Loewen JL, Heuston S, Helgeson C, White HS, Wilcox KS, West PJ (2017) Corneal kindled C57BL/6 mice exhibit saturated dentate gyrus long-term potentiation and associated memory deficits in the absence of overt neuron loss. Neurobiol Dis 105:221–234. https://doi.org/10.1016/j.nbd.2017.06.006 CrossRefGoogle Scholar
- Suzuki G et al (2007) Pharmacological characterization of a new, orally active and potent allosteric metabotropic glutamate receptor 1 antagonist, 4-[1-(2-fluoropyridin-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methyl- 3,6-dihydropyridine-1(2H)-carboxamide (FTIDC). J Pharmacol Exp Ther 321:1144–1153. https://doi.org/10.1124/jpet.106.116574 CrossRefGoogle Scholar
- Thompson PJ (1991) Memory function in patients with epilepsy. Adv Neurol 55:369–384Google Scholar
- Vasil’ev DS, Tumanova NL, Zhuravin IA, Kim KK, Lukomskaya N, Magazanik LG, Zaitsev AV (2014) Morphofunctional changes in field CA1 of the rat hippocampus after pentylenetetrazole and lithium-pilocarpine induced seizures. J Evol Biochem Physiol 50:531–538. https://doi.org/10.1134/S0022093014060088 CrossRefGoogle Scholar
- Weng SM, McLeod F, Bailey ME, Cobb SR (2011) Synaptic plasticity deficits in an experimental model of rett syndrome: long-term potentiation saturation and its pharmacological reversal. Neuroscience 180:314–321. https://doi.org/10.1016/j.neuroscience.2011.01.061 CrossRefGoogle Scholar
- Wolf DC, Bueno-Junior LS, Lopes-Aguiar C, Do Val Da Silva RA, Kandratavicius L, Leite JP (2016) The frequency of spontaneous seizures in rats correlates with alterations in sensorimotor gating, spatial working memory, and parvalbumin expression throughout limbic regions. Neuroscience 312:86–98. https://doi.org/10.1016/j.neuroscience.2015.11.008 CrossRefGoogle Scholar