Role of inositol 1, 4, 5-trisphosphate receptors in the postsynaptic expression of guinea pig hippocampal mossy fiber depotentiation

Long-term potentiation (LTP) at hippocampal mossy fiber-CA3 pyramidal neuron synapses was induced in the field excitatory postsynaptic potential (EPSP) by the delivery of HFS (a tetanus of two trains of 100 pulses at 100 Hz with a 10 s interval) and was reversed (depotentiated) by a train of LFS of 1000 pulses at 2 Hz applied 60 min later. This depotentiation was triggered by activation of inositol 1, 4, 5-trisphosphate receptors (IP3Rs) during HFS, which may increase the postsynaptic intracellular Ca2+ concentration, leading to a cellular process responsible for modification of LTP expression at mossy fiber-CA3 synapses. Furthermore, we found that activation of IP3Rs or protein phosphatase during LFS was required for the reversal of LTP expressed at mossy fiber-CA3 synapses. These results suggest that, in hippocampal mossy fiber-CA3 neuron synapses, activation of IP3Rs by a preconditioning HFS results in modulation of IP3R activation and/or postsynaptic protein phosphorylation during a subsequent LFS, leading to a decrease in the field EPSP and the erasure of LTP.

Research highlights
► Activation of IP3Rs during the HFS triggers the reversal of LTP in CA3 neurons.
► Activation of IP3Rs during the LFS is involved in the mechanism for the reversal of LTP.
► IP3Rs activated during the HFS may modulate the degree of activation of IP3Rs during the LFS.
► IP3Rs activated during the HFS may decide whether LTP is reversed or not.