Developmentally regulated actions of alcohol on hippocampal glutamatergic transmission.

Détails

ID Serval
serval:BIB_A27D6026559B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Developmentally regulated actions of alcohol on hippocampal glutamatergic transmission.
Périodique
The Journal of neuroscience
Auteur(s)
Mameli M., Zamudio P.A., Carta M., Valenzuela C.F.
ISSN
1529-2401 (Electronic)
ISSN-L
0270-6474
Statut éditorial
Publié
Date de publication
31/08/2005
Peer-reviewed
Oui
Volume
25
Numéro
35
Pages
8027-8036
Langue
anglais
Notes
Publication types: Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
Publication Status: ppublish
Résumé
Ethanol exposure during fetal development is a leading cause of learning disabilities. Studies suggest that it alters learning and memory by permanently damaging the hippocampus. It is generally assumed that this is mediated, in part, via alterations in glutamatergic transmission. Although NMDA receptors are presumed to be the most sensitive targets of ethanol in immature neurons, this issue has not been explored in the developing hippocampus. We performed whole-cell patch-clamp recordings in hippocampal slices from neonatal rats. Unexpectedly, we found that acute ethanol (10-50 mM) exposure depresses inward currents elicited by local application of exogenous AMPA, but not NMDA, in CA3 pyramidal neurons. These findings revealed a direct effect of ethanol on postsynaptic AMPA receptors. Ethanol significantly decreased the amplitude of both AMPA and NMDA receptor-mediated EPSCs evoked by electrical stimulation. This effect was associated with an increase in the paired-pulse ratio and a decrease in the frequency of miniature EPSCs driven by depolarization of axonal terminals. These findings demonstrate that ethanol also acts at the presynaptic level. Omega-conotoxin-GVIA occluded the effect of ethanol on NMDA EPSCs, indicating that ethanol decreases glutamate release via inhibition of N-type voltage-gated Ca2+ channels. In more mature rats, ethanol did not affect the probability of glutamate release or postsynaptic AMPA receptor-mediated currents, but it did inhibit NMDA-mediated currents. We conclude that the mechanism by which ethanol inhibits glutamatergic transmission is age dependent and challenge the view that postsynaptic NMDA receptors are the primary targets of ethanol early in development.

Mots-clé
Animals, Animals, Newborn, Dose-Response Relationship, Drug, Ethanol/pharmacology, Excitatory Amino Acid Agonists/pharmacology, Glutamic Acid/physiology, Hippocampus/drug effects, Hippocampus/growth & development, In Vitro Techniques, Rats, Rats, Sprague-Dawley, Receptors, AMPA/agonists, Receptors, AMPA/physiology, Receptors, N-Methyl-D-Aspartate/agonists, Receptors, N-Methyl-D-Aspartate/physiology, Synaptic Transmission/drug effects, Synaptic Transmission/physiology
Pubmed
Web of science
Open Access
Oui
Création de la notice
03/02/2017 11:21
Dernière modification de la notice
20/08/2019 15:08
Données d'usage