title: Aberrant NMDA-dependent LTD after perinatal ethanol exposure in young adult rat hippocampus.
abstract: Irreversible cognitive deficits induced by ethanol exposure during fetal life have been ascribed to a lower NMDA-dependent synaptic long-term potentiation (LTP) in the hippocampus. Whether NMDA-dependent long-term depression (LTD) may also play a critical role in those deficits remains unknown. Here, we show that in vitro LTD induced with paired-pulse low frequency stimulation is enhanced in CA1 hippocampus field of young adult rats exposed to ethanol during brain development. Furthermore, single pulse low frequency stimulation, ineffective at this age (LFS600), induced LTD after ethanol exposure accompanied with a stronger response than controls during LFS600, thus revealing an aberrant form of activity-dependent plasticity at this age. Blocking NMDA receptor or GluN2B containing NMDA receptor prevented both the stronger response during LFS600 and LTD whereas Zinc, an antagonist of GluN2A containing NMDA receptor, was ineffective on both responses. In addition, LFS600-induced LTD was revealed in controls only with a reduced-Mg(2+) medium. In whole dissected hippocampus CA1 field, perinatal ethanol exposure increased GluN2B subunit expression in the synaptic compartment whereas GluN2A was unaltered. Using pharmacological tools, we suggest that LFS600 LTD was of synaptic origin. Altogether, we describe a new mechanism by which ethanol exposure during fetal life induces a long-term alteration of synaptic plasticity involving NMDA receptors, leading to an aberrant LTD. We suggest this effect of ethanol may reflect a delayed maturation of the synapse and that aberrant LTD may also participates to long-lasting cognitive deficits in fetal alcohol spectrum disorder.
authors.forename: Myriam
authors.initials: M
authors.lastname: Kervern
authors.forename: Benoît
authors.initials: B
authors.lastname: Silvestre de Ferron
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Alaux-Cantin
authors.forename: Olena
authors.initials: O
authors.lastname: Fedorenko
authors.forename: Johann
authors.initials: J
authors.lastname: Antol
authors.forename: Mickael
authors.initials: M
authors.lastname: Naassila
authors.affiliation: INSERM ERi 24 - GRAP, Groupe de Recherche sur l'Alcool et les Pharmacodépendances, C.U.R.S., UPJV, Amiens, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Pierrefiche
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000633:toxicity*; D004558:Electric Stimulation; D000431:Ethanol / Q000633:toxicity*; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology*; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*
chemical_list: D002492:Central Nervous System Depressants; D018683:Excitatory Amino Acid Agents; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; C120673:benzyloxyaspartate; D001224:Aspartic Acid; D000431:Ethanol; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione
keywords: GluN2B; NMDA; in utero ethanol; slice