{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:29:25Z","timestamp":1790710165118,"version":"4.1.0"},"reference-count":83,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2021,12,12]],"date-time":"2021-12-12T00:00:00Z","timestamp":1639267200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["21-15-00430"],"award-info":[{"award-number":["21-15-00430"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Status epilepticus (SE) causes persistent abnormalities in the functioning of neuronal networks, often resulting in worsening epileptic seizures. Many details of cellular and molecular mechanisms of seizure-induced changes are still unknown. The lithium\u2013pilocarpine model of epilepsy in rats reproduces many features of human temporal lobe epilepsy. In this work, using the lithium\u2013pilocarpine model in three-week-old rats, we examined the morphological and electrophysiological changes in the hippocampus within a week following pilocarpine-induced seizures. We found that almost a third of the neurons in the hippocampus and dentate gyrus died on the first day, but this was not accompanied by impaired synaptic plasticity at that time. A diminished long-term potentiation (LTP) was observed following three days, and the negative effect of SE on plasticity increased one week later, being accompanied by astrogliosis. The attenuation of LTP was caused by the weakening of N-methyl-D-aspartate receptor (NMDAR)-dependent signaling. NMDAR-current was more than two-fold weaker during high-frequency stimulation in the post-SE rats than in the control group. Application of glial transmitter D-serine, a coagonist of NMDARs, allows the enhancement of the NMDAR-dependent current and the restoration of LTP. These results suggest that the disorder of neuron\u2013astrocyte interactions plays a critical role in the impairment of synaptic plasticity.<\/jats:p>","DOI":"10.3390\/ijms222413355","type":"journal-article","created":{"date-parts":[[2021,12,13]],"date-time":"2021-12-13T01:28:11Z","timestamp":1639358891000},"page":"13355","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Impairments of Long-Term Synaptic Plasticity in the Hippocampus of Young Rats during the Latent Phase of the Lithium-Pilocarpine Model of Temporal Lobe Epilepsy"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7049-4478","authenticated-orcid":false,"given":"Tatyana Y.","family":"Postnikova","sequence":"first","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, Saint Petersburg 194223, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgy P.","family":"Diespirov","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, Saint Petersburg 194223, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dmitry V.","family":"Amakhin","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, Saint Petersburg 194223, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizaveta N.","family":"Vylekzhanina","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, Saint Petersburg 194223, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena B.","family":"Soboleva","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, Saint Petersburg 194223, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4503-0647","authenticated-orcid":false,"given":"Aleksey V.","family":"Zaitsev","sequence":"additional","affiliation":[{"name":"Sechenov Institute of Evolutionary Physiology and Biochemistry of RAS, Saint Petersburg 194223, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1212\/WNL.0000000000000610","article-title":"The global burden of neurologic diseases","volume":"83","author":"Chin","year":"2014","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1002\/hbm.23887","article-title":"Mapping the structural and functional network architecture of the medial temporal lobe using 7T MRI","volume":"39","author":"Shah","year":"2018","journal-title":"Hum. Brain Mapp."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1038\/nrn1607","article-title":"The organization of recent and remote memories","volume":"6","author":"Frankland","year":"2005","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0079-6123(02)35023-4","article-title":"Hippocampal neuron damage in human epilepsy: Meyer\u2019s hypothesis revisited","volume":"135","author":"Mathern","year":"2002","journal-title":"Prog. Brain Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/S1474-4422(04)00906-8","article-title":"Chronic epilepsy and cognition","volume":"3","author":"Elger","year":"2004","journal-title":"Lancet Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S1474-4422(10)70310-0","article-title":"Mechanisms of epileptogenesis and potential treatment targets","volume":"10","author":"Lukasiuk","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"112044","DOI":"10.1016\/j.bbr.2019.112044","article-title":"Impairments in cognitive functions and emotional and social behaviors in a rat lithium-pilocarpine model of temporal lobe epilepsy","volume":"372","author":"Smolensky","year":"2019","journal-title":"Behav. Brain Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"18284","DOI":"10.3390\/ijms140918284","article-title":"Experimental Models of Status Epilepticus and Neuronal Injury for Evaluation of Therapeutic Interventions","volume":"14","author":"Reddy","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1111\/epi.12418","article-title":"de Do seizures and epileptic activity worsen epilepsy and deteriorate cognitive function?","volume":"54","author":"Avanzini","year":"2013","journal-title":"Epilepsia"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/nrneurol.2011.3","article-title":"The neurobiology of cognitive disorders in temporal lobe epilepsy","volume":"7","author":"Bell","year":"2011","journal-title":"Nat. Rev. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1146\/annurev.neuro.23.1.649","article-title":"Synaptic plasticity and memory: An evaluation of the hypothesis","volume":"23","author":"Martin","year":"2000","journal-title":"Annu. Rev. Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/sj.npp.1301559","article-title":"Synaptic Plasticity: Multiple Forms, Functions, and Mechanisms","volume":"33","author":"Citri","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1038\/361031a0","article-title":"A synaptic model of memory: Long-term potentiation in the hippocampus","volume":"361","author":"Bliss","year":"1993","journal-title":"Nature"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4363","DOI":"10.1073\/pnas.89.10.4363","article-title":"Homosynaptic long-term depression in area CA1 of hippocampus and effects of N-methyl-D-aspartate receptor blockade","volume":"89","author":"Dudek","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.neuroscience.2018.12.029","article-title":"Changes in Functional Properties of Rat Hippocampal Neurons Following Pentylenetetrazole-induced Status Epilepticus","volume":"399","author":"Postnikova","year":"2019","journal-title":"Neuroscience"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"108320","DOI":"10.1016\/j.yebeh.2021.108320","article-title":"Down-regulation of AMPA receptors and long-term potentiation during early epileptogenesis","volume":"124","author":"Orfila","year":"2021","journal-title":"Epilepsy Behav."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1097\/WNR.0000000000000656","article-title":"Status epilepticus alters hippocampal long-term synaptic potentiation in a rat lithium-pilocarpine model","volume":"27","author":"Kryukov","year":"2016","journal-title":"Neuroreport"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"215","DOI":"10.3389\/fnmol.2018.00215","article-title":"Astrocytic Atrophy Following Status Epilepticus Parallels Reduced Ca2+ Activity and Impaired Synaptic Plasticity in the Rat Hippocampus","volume":"11","author":"Plata","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.yebeh.2010.02.008","article-title":"Time-dependent changes in learning ability and induction of long-term potentiation in the lithium\u2013pilocarpine-induced epileptic mouse model","volume":"17","author":"Zhang","year":"2010","journal-title":"Epilepsy Behav."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6592038","DOI":"10.1155\/2016\/6592038","article-title":"Status Epilepticus Enhances Depotentiation after Fully Established LTP in an NMDAR-Dependent but GluN2B-Independent Manner","volume":"2016","author":"Guli","year":"2016","journal-title":"Neural Plast."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.nbd.2012.12.011","article-title":"Enhanced NMDA receptor-dependent LTP in the epileptic CA1 area via upregulation of NR2B","volume":"54","author":"Tokay","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0014-4886(03)00086-4","article-title":"Neuronal and glial pathological changes during epileptogenesis in the mouse pilocarpine model","volume":"182","author":"Borges","year":"2003","journal-title":"Exp. Neurol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1016\/j.neuint.2007.10.021","article-title":"Seizures in the developing brain: Cellular and molecular mechanisms of neuronal damage, neurogenesis and cellular reorganization","volume":"52","author":"Holopainen","year":"2008","journal-title":"Neurochem. Int."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1002\/hipo.1076","article-title":"Resistance of immature hippocampus to morphologic and physiologic alterations following status epilepticus or kindling","volume":"11","author":"Haas","year":"2001","journal-title":"Hippocampus"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"8382","DOI":"10.1523\/JNEUROSCI.18-20-08382.1998","article-title":"Patterns of status epilepticus-induced neuronal injury during development and long-term consequences","volume":"18","author":"Sankar","year":"1998","journal-title":"J. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.jneumeth.2008.04.019","article-title":"The pilocarpine model of temporal lobe epilepsy","volume":"172","author":"Curia","year":"2008","journal-title":"J. Neurosci. Methods"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.neubiorev.2021.08.020","article-title":"The pilocarpine model of mesial temporal lobe epilepsy: Over one decade later, with more rodent species and new investigative approaches","volume":"130","author":"Biagini","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1111\/j.1528-1167.2005.43804.x","article-title":"Entorhinal Cortex Involvement in Human Mesial Temporal Lobe Epilepsy: An Electrophysiologic and Volumetric Study","volume":"46","author":"Bartolomei","year":"2005","journal-title":"Epilepsia"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1097\/00005072-199702000-00011","article-title":"Human fascia dentata anatomy and hippocampal neuron densities differ depending on the epileptic syndrome and age at first seizure","volume":"56","author":"Mathern","year":"1997","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1111\/j.1528-1167.2006.00455.x","article-title":"Status Epilepticus in 12-day-old Rats Leads to Temporal Lobe Neurodegeneration and Volume Reduction: A Histologic and MRI Study","volume":"47","author":"Nairismagi","year":"2006","journal-title":"Epilepsia"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/S1474-4422(06)70626-3","article-title":"Effects of seizures on developmental processes in the immature brain","volume":"5","author":"Holmes","year":"2006","journal-title":"Lancet Neurol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.3389\/fneur.2020.591690","article-title":"Astrocytes as Guardians of Neuronal Excitability: Mechanisms Underlying Epileptogenesis","volume":"11","author":"Verhoog","year":"2020","journal-title":"Front. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1111\/j.1528-1167.2008.01491.x","article-title":"Rapid astrocyte and microglial activation following pilocarpine-induced seizures in rats","volume":"49","author":"Shapiro","year":"2008","journal-title":"Epilepsia"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2730","DOI":"10.1007\/s11064-017-2276-y","article-title":"Phase-Dependent Astroglial Alterations in Li\u2013Pilocarpine-Induced Status Epilepticus in Young Rats","volume":"42","author":"Vizuete","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuroscience.2021.05.035","article-title":"Alterations in mRNA and protein expression of glutamate receptor subunits following pentylenetetrazole-induced acute seizures in young rats","volume":"468","author":"Kovalenko","year":"2021","journal-title":"Neuroscience"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.neulet.2018.08.047","article-title":"Alterations in mRNA expression of glutamate receptor subunits and excitatory amino acid transporters following pilocarpine-induced seizures in rats","volume":"686","author":"Zubareva","year":"2018","journal-title":"Neurosci. Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1134\/S002209302103008X","article-title":"Synaptic Dysfunction in Epilepsy","volume":"57","author":"Zaitsev","year":"2021","journal-title":"J. Evol. Biochem. Physiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.mcn.2018.05.002","article-title":"Functional organization of postsynaptic glutamate receptors","volume":"91","author":"Scheefhals","year":"2018","journal-title":"Mol. Cell. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.neuropharm.2009.01.002","article-title":"Metabotropic glutamate receptor-dependent long-term potentiation","volume":"56","author":"Anwyl","year":"2009","journal-title":"Neuropharmacology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"9840","DOI":"10.1523\/JNEUROSCI.1000-18.2018","article-title":"Biphasic modulation of NMDA receptor function by metabotropic glutamate receptors","volume":"38","author":"McLaughlin","year":"2018","journal-title":"J. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"14423","DOI":"10.1096\/fj.201900417R","article-title":"The receptor-receptor interaction between mGluR1 receptor and NMDA receptor: A potential therapeutic target for protection against ischemic stroke","volume":"33","author":"Lai","year":"2019","journal-title":"FASEB J."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s10571-018-00647-3","article-title":"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","volume":"39","author":"Postnikova","year":"2019","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Postnikova, T.Y., Griflyuk, A.V., Amakhin, D.V., Kovalenko, A.A., Soboleva, E.B., Zubareva, O.E., and Zaitsev, A.V. (2021). Early Life Febrile Seizures Impair Hippocampal Synaptic Plasticity in Young Rats. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22158218"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"264","DOI":"10.3389\/fncel.2017.00264","article-title":"Alterations in Properties of Glutamatergic Transmission in the Temporal Cortex and Hippocampus Following Pilocarpine-Induced Acute Seizures in Wistar Rats","volume":"11","author":"Amakhin","year":"2017","journal-title":"Front. Cell. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1038\/nrn.2017.24","article-title":"NMDA receptors: Linking physiological output to biophysical operation","volume":"18","author":"Iacobucci","year":"2017","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1615\/CritRevNeurobiol.v18.i1-2.80","article-title":"Hippocampal Long-Term Synaptic Plasticity and Signal Amplification of NMDA Receptors","volume":"18","author":"MacDonald","year":"2006","journal-title":"Crit. Rev. Neurobiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"11685","DOI":"10.1523\/JNEUROSCI.3035-08.2008","article-title":"Extrasynaptic NR2D-Containing NMDARs Are Recruited to the Synapse during LTP of NMDAR-EPSCs","volume":"28","author":"Harney","year":"2008","journal-title":"J. Neurosci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1528-1167.2006.00416.x","article-title":"A brief period of epileptiform activity strengthens excitatory synapses in the rat hippocampus in vitro","volume":"47","author":"Debanne","year":"2006","journal-title":"Epilepsia"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.nbd.2011.02.012","article-title":"Pilocapine alters NMDA receptor expression and function in hippocampal neurons: NADPH oxidase and ERK1\/2 mechanisms","volume":"42","author":"Mastroberardino","year":"2011","journal-title":"Neurobiol. Dis."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.nbd.2017.03.017","article-title":"Enhanced AMPA receptor-mediated neurotransmission on CA1 pyramidal neurons during status epilepticus","volume":"103","author":"Joshi","year":"2017","journal-title":"Neurobiol. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1113\/jphysiol.2003.052662","article-title":"Epileptiform activity in rat hippocampus strengthens excitatory synapses","volume":"554","author":"Abegg","year":"2004","journal-title":"J. Physiol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"486","DOI":"10.3389\/fncel.2018.00486","article-title":"Seizure-Induced Potentiation of AMPA Receptor-Mediated Synaptic Transmission in the Entorhinal Cortex","volume":"12","author":"Amakhin","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1038\/nn1678","article-title":"Transient incorporation of native GluR2-lacking AMPA receptors during hippocampal long-term potentiation","volume":"9","author":"Plant","year":"2006","journal-title":"Nat. Neurosci."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.neuroscience.2016.04.024","article-title":"Changes of ampa receptor properties in the neocortex and hippocampus following pilocarpine-induced status epilepticus in rats","volume":"327","author":"Malkin","year":"2016","journal-title":"Neuroscience"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.conb.2011.09.008","article-title":"Posttranslational regulation of AMPA receptor trafficking and function","volume":"22","author":"Lu","year":"2012","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"955","DOI":"10.1038\/35016089","article-title":"Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity","volume":"405","author":"Lee","year":"2000","journal-title":"Nature"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/nrn3504","article-title":"NMDA receptor subunit diversity: Impact on receptor properties, synaptic plasticity and disease","volume":"14","author":"Paoletti","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.nbd.2012.07.013","article-title":"Thiol oxidation and altered NR2B\/NMDA receptor functions in in vitro and in vivo pilocarpine models: Implications for epileptogenesis","volume":"49","author":"Mastroberardino","year":"2013","journal-title":"Neurobiol. Dis."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.brainresbull.2015.04.002","article-title":"NMDA receptor NR2B subunits contribute to PTZ-kindling-induced hippocampal astrocytosis and oxidative stress","volume":"114","author":"Zhu","year":"2015","journal-title":"Brain Res. Bull."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.expneurol.2016.05.034","article-title":"Blocking GluN2B subunits reverses the enhanced seizure susceptibility after prolonged febrile seizures with a wide therapeutic time-window","volume":"283","author":"Chen","year":"2016","journal-title":"Exp. Neurol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.neuron.2014.03.030","article-title":"Extrasynaptic NMDA receptor involvement in central nervous system disorders","volume":"82","author":"Parsons","year":"2014","journal-title":"Neuron"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Franchini, L., Carrano, N., Di Luca, M., and Gardoni, F. (2020). Synaptic GluN2A-Containing NMDA Receptors: From Physiology to Pathological Synaptic Plasticity. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041538"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Li, R., Huang, F.S., Abbas, A.K., and Wigstr\u00f6m, H. (2007). Role of NMDA receptor subtypes in different forms of NMDA-dependent synaptic plasticity. BMC Neurosci., 8.","DOI":"10.1186\/1471-2202-8-55"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1126\/science.1096615","article-title":"Role of NMDA Receptor Subtypes in Governing the Direction of Hippocampal Synaptic Plasticity","volume":"304","author":"Liu","year":"2004","journal-title":"Science"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"7821","DOI":"10.1523\/JNEUROSCI.1697-04.2004","article-title":"Differential roles of NR2A and NR2B-containing NMDA receptors in cortical long-term potentiation and long-term depression","volume":"24","author":"Massey","year":"2004","journal-title":"J. Neurosci."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.neuropharm.2006.07.013","article-title":"Differential roles of NR2A and NR2B-containing NMDA receptors in LTP and LTD in the CA1 region of two-week old rat hippocampus","volume":"52","author":"Bartlett","year":"2007","journal-title":"Neuropharmacology"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"8764","DOI":"10.1523\/JNEUROSCI.1014-09.2009","article-title":"Metaplastic regulation of long-term potentiation\/long-term depression threshold by activity-dependent changes of NR2A\/NR2B ratio","volume":"29","author":"Xu","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1124\/pr.109.002451","article-title":"Glutamate Receptor Ion Channels: Structure, Regulation, and Function","volume":"62","author":"Traynelis","year":"2010","journal-title":"Pharmacol. Rev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2835","DOI":"10.1152\/jn.2000.83.5.2835","article-title":"Synaptically Released Glutamate Does Not Overwhelm Transporters on Hippocampal Astrocytes During High-Frequency Stimulation","volume":"83","author":"Diamond","year":"2000","journal-title":"J. Neurophysiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"10404","DOI":"10.1523\/JNEUROSCI.2066-16.2016","article-title":"Glutamate Clearance Is Locally Modulated by Presynaptic Neuronal Activity in the Cerebral Cortex","volume":"36","author":"Armbruster","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"232105","DOI":"10.1155\/2014\/232105","article-title":"Astrocyte-Synapse Structural Plasticity","volume":"2014","author":"Bernardinelli","year":"2014","journal-title":"Neural Plast."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.nbd.2010.07.018","article-title":"Increased coupling and altered glutamate transport currents in astrocytes following kainic-acid-induced status epilepticus","volume":"40","author":"Takahashi","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1007\/s40263-020-00764-y","article-title":"Neurobiology, Functions, and Relevance of Excitatory Amino Acid Transporters (EAATs) to Treatment of Refractory Epilepsy","volume":"34","author":"Zaitsev","year":"2020","journal-title":"CNS Drugs"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"113196","DOI":"10.1016\/j.expneurol.2020.113196","article-title":"Ultrastructural and functional changes at the tripartite synapse during epileptogenesis in a model of temporal lobe epilepsy","volume":"326","author":"Clarkson","year":"2020","journal-title":"Exp. Neurol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/j.bpj.2019.07.057","article-title":"Ca2+-Dependent Inactivation of GluN2A and GluN2B NMDA Receptors Occurs by a Common Kinetic Mechanism","volume":"118","author":"Iacobucci","year":"2020","journal-title":"Biophys. J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/325529a0","article-title":"Glycine potentiates the NMDA response in cultured mouse brain neurons","volume":"325","author":"Johnson","year":"1987","journal-title":"Nature"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1113\/jphysiol.1990.sp018215","article-title":"A kinetic analysis of the modulation of N-methyl-D-aspartic acid receptors by glycine in mouse cultured hippocampal neurones","volume":"428","author":"Benveniste","year":"1990","journal-title":"J. Physiol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1085\/jgp.201411302","article-title":"Glycine-dependent activation of NMDA receptors","volume":"145","author":"Cummings","year":"2015","journal-title":"J. Gen. Physiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.neuropharm.2015.08.031","article-title":"Glycine transporter 1 is a target for the treatment of epilepsy","volume":"99","author":"Shen","year":"2015","journal-title":"Neuropharmacology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1111\/j.1582-4934.2008.00357.x","article-title":"Glycinergic tonic inhibition of hippocampal neurons with depolarizing GABAergic transmission elicits histopathological signs of temporal lobe epilepsy","volume":"12","author":"Eichler","year":"2008","journal-title":"J. Cell. Mol. Med."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1038\/nature08673","article-title":"Long-term potentiation depends on release of d-serine from astrocytes","volume":"463","author":"Henneberger","year":"2010","journal-title":"Nature"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/0006-8993(83)90676-5","article-title":"Long-term potentiation phenomena in the rat limbic forebrain","volume":"260","author":"Racine","year":"1983","journal-title":"Brain Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3178","DOI":"10.1523\/JNEUROSCI.10-09-03178.1990","article-title":"Voltage dependence of NMDA-activated macroscopic conductances predicted by single-channel kinetics","volume":"10","author":"Jahr","year":"1990","journal-title":"J. Neurosci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/24\/13355\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:46:04Z","timestamp":1760168764000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/24\/13355"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,12]]},"references-count":83,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["ijms222413355"],"URL":"https:\/\/doi.org\/10.3390\/ijms222413355","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,12]]}}}