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

Abstract

We investigated the role of inositol 1, 4, 5-trisphosphate receptors (IP3Rs), activated during preconditioning low-frequency afferent stimulation (LFS), in the subsequent induction of long-term potentiation (LTP) in CA3 neurons in hippocampal slices from mature guinea pigs. Induction of LTP in the field excitatory postsynaptic potential (EPSP) by the delivery of high-frequency stimulation (HFS, a tetanus of two trains of 100 pulses at 100Hz with a 10s interval) to mossy fiber-CA3 neuron synapses was suppressed when CA3 synapses were preconditioned by the LFS of 1000 pulses at 2Hz and this effect was inhibited when the LFS preconditioning was performed in the presence of an IP3R antagonist or a protein phosphatase inhibitor. Furthermore, activation of group 1 metabotropic glutamate receptors (mGluRs) during HFS canceled the effects of an IP3R antagonist given during preconditioning LFS on the subsequent LTP induction at mossy fiber-CA3 synapses. These results suggest that, in hippocampal mossy fiber-CA3 neuron synapses, activation of IP3Rs during a preconditioning LFS results in dephosphorylation events that lead to failure of the HFS to induce subsequent LTP.