Abstract
NMDA transmission: first, record evoked responses at +40mV in presence of magnesium, or record at a holding potential of −60mV in Mg2+ free-ACSF in the presence of NBQX to block AMPA transmission. Activation of 5-HT2A receptors induced no modifications on the NMDA evoked response by using the depolarizing protocol, however 5-HT2A receptors stimulation elicited a reversible strong potentiation when experiments were performed with the second recording protocol. We hypothesized that this NMDA facilitation could be due to the activation of presynaptic NMDA receptors leading to an increase of glutamate release. We confirmed this hypothesis by recording AMPA mediated miniature EPSCs. DOI provoked an increase in miniature frequency only in Mg2+ free-ACSF, reflecting a presynaptic modification. Further supporting the involvement of presynaptic NMDA receptors, this effect was blocked by the NMDA antagonist AP5. All the effects of DOI were prevented by ketanserin, a 5-HT2A receptor antagonist, as well as by the genetic invalidation of 5-HT2A receptors. We started to examine the effect of 5-HT2A receptors activation on AMPA transmission. DOI application induced a robust depression of AMPA transmission of about 30%, this effect was lasting during 45 min of wash. Conclusion: Here, we showed that activation of 5-HT2A receptors modulates synaptic transmission by inducing a depression of AMPA currents at the postsynaptic site and an activation of presynaptic NMDA receptors. Collectively, these data suggest that 5-HT2A receptors exert a pleiotropic action on glutamatergic transmission.
Published Version
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