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The role of inositol 1, 4, 5-trisphosphate receptors (IP3Rs) in long-termpotentiation (LTP) and long-term depression (LTD) was studied in CA1 neuronsin guinea pig hippocampal slices. In standard solution, short tetanicstimulation consisting of 15 pulses at 100 Hz induced LTP, while three shorttrains of low-frequency stimulation (LFS; 200 pulses at 1 Hz) at 18-minintervals or one long train of LFS (1000 pulses at 1 Hz) induced stable LTD inboth the slope of the field EPSP (S-EPSP) and the amplitude of the populationspike (A-PS). Bath application of 2-aminoethoxydiphenyl borate (2-APB), anIP3R antagonist, or of α-methyl-4-carboxyphenylglycine (MCPG), awide-spectrum metabotropic glutamate receptor antagonist, during weak tetanicstimulation significantly increased the magnitude of the LTP in both theS-EPSP and A-PS. Three short trains of LFS or one long train of LFS deliveredin the presence of 2-APB or MCPG did not induce LTD, but elicited LTP. Basedon these results, we conclude that, in hippocampal CA1 neurons, IP3Rs play animportant role in synaptic plasticity by attenuating LTP and facilitatingLTD.

Involvement of IP3 receptors in LTP and LTD induction in guinea pig hippocampal CA1 neurons