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 IP(3)R1(-/-) 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-D-aspartate receptor (NMDAR)-dependent LTP, the effect of tetanus was tested in the present of the NMDAR antagonist, D,L-AP5 (50 microM); 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 microM) 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.