Developmentally regulated actions of alcohol on hippocampal glutamatergic transmission
Journal of Neuroscience. 2005-08-31; 25(35): 8027-8036
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1. J Neurosci. 2005 Aug 31;25(35):8027-36.
Developmentally regulated actions of alcohol on hippocampal glutamatergic
Mameli M(1), Zamudio PA, Carta M, Valenzuela CF.
(1)Department of Neurosciences, University of New Mexico Health Sciences Center,
Albuquerque, New Mexico 87131, USA.
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
PMID: 16135760 [Indexed for MEDLINE]