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 10s 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 Ca(2+) 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.