The cellular mechanisms that mediate spike-timing dependent plasticity (STDP) are largely unknown. We investigated in vitro in CA1 pyramidal neurons the contribution of AMPA and NMDA components of Schaffer collateral (SC) EPSPs (EPSP_AMPA and EPSP_NMDA) and of the back-propagating action potential (BAP) to the LTP induced by a STDP protocol that consisted in pairing an EPSP and a BAP. Transient blockade of EPSP_AMPA with CNQX during the STDP protocol prevented LTP. Contrastingly LTP was induced under transient inhibition of EPSP_AMPA by combining SC stimulation, an imposed EPSP_AMPA-like depolarization and BAP, or by coupling the EPSP_NMDA evoked under sustained depolarization ( -40mV) and BAP. In Mg²⁺-free solution EPSP_NMDA and BAP also produced LTP. Suppression of EPSP_NMDA or BAP always prevented LTP. Thus, activation of NMDARs and BAP are required but not sufficient because AMPAR activation is also obligatory for STDP. However a transient depolarization of another origin that unblocks NMDARs and a BAP may also trigger LTP.