SY13-4FETAL ALCOHOL EXPOSURE INDUCES A LONG-TERM ALTERATION OF NMDA-DEPENDENT SYNAPTIC PLASTICITY, LEADING TO AN ABERRANT LONG TERM DEPRESSION
Résumé
Ethanol exposure during fetal life can induce irreversible cognitive deficits. These deficits have been ascribed so far to a lower NMDA-dependent synaptic long-term potentiation (LTP) in the hippocampus and whether NMDA-dependent long-term depression (LTD) may also play a critical role in those deficits remained unknown. In the present study we showed that in vitro LTD is enhanced in CA1 hippocampus field of young adult rats exposed to ethanol during brain development. Using western-blot and pharmacological tools we studied the mode of action of ethanol to induce such aberrant LTD. After ethanol the response to electrical stimulation inducing LTD was higher than in control slices and blocked with AP-5 which also had an effect on baseline recording, suggesting a higher role of the NMDA component in the excitatory transmission in CA1 field. Furthermore, aberrant LTD was ifenprodil sensitive and insensitive to zinc, revealing a predominant role for GluN2B subunit containing NMDA receptors. In addition, GluN2B subunit expression was specifically increased in the synapse and we demonstrated that aberrant LTD was of synaptic origin and does not involved perisynaptic NMDA receptors.
Our study suggests that EtOH during brain development induces a reorganization of the excitatory synapse including then more NMDA receptors containing the GluN2B subunit, leading to an enhanced response during electrical stimulation responsible for induction of LTD of synaptic origin. This novel mechanism of prenatal ethanol exposure on synaptic plasticity revealed that aberrant LTD, in addition to LTP disturbance, may participates to long-lasting cognitive deficits in fetal alcohol spectrum disorders.