Neuronal plasticity in hippocampal mossy fiber–CA3 synapses of mice lacking the inositol-1,4,5-trisphosphate type 1 receptor

In the present study, we used inositol-1,4,5-trisphosphate (IP₃) type 1 receptor (IP₃R1) knockout mice to examine the role of this receptor in the induction of LTP, LTD, and DP at mossy fiber–CA3 synapses. No difference in synaptically induced field-EPSPs was seen between the wild-type (IP₃R1^+/+) and IP₃R1 knockout mice (IP₃R1^−/−), showing that basic synaptic transmission does not involve IP₃R1 activation. Tetanus induced LTP in both wild-type and IP₃R1^−/− mice, but the magnitude of LTP was significantly greater in IP₃R1^−/− mice (149.8±3.5%, mean±S.E.M., n=15) than in wild-type mice (132.4±1.5%, n=17), suggesting that the IP₃R1 has a suppressive effect on LTP induction. To determine whether this effect involved N-methyl- -aspartate receptor (NMDAR)-dependent LTP, the effect of tetanus was tested in the present of the NMDAR antagonist, -AP5 (50 μM); under these conditions, the LTP in both IP₃R1^−/− and IP₃R1^+/+ mice was not significantly reduced. In addition, group I mGluR activation was shown to be necessary for LTP induction, as the LTP was almost blocked by the group I mGluR antagonist, RS-4CPG (500 μM) in both IP₃R1^−/− (117.6±1.7%, n=8) and IP₃R1^+/+ (116.9±1.8%, n=5) mice. The IP₃R1 also plays an essential role in LTD induction, as low-frequency stimulation (LFS) failed to induce LTD in the mutant mice (104.5±2.1%, n=10). DP was induced in both IP₃R1^−/− and wild-type mice.