Suppressive effect of preconditioning low-frequency stimulation on subsequent induction of long-term potentiation by high frequency stimulation in hippocampal CA3 neurons

► Induction of LTP was suppressed when CA3 synapses were preconditioned by 2 Hz LFS. ► LTP was induced when the LFS preconditioning was performed in an IP3Rs antagonist. ► LTP was induced when CA3 synapses were preconditioned in a phosphatase inhibitor. ► Activation of IP3Rs during a preconditioning LFS results in dephosphorylation events. ► Dephosphorylation events lead to failure of HFS to induce subsequent LTP.