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 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.
Itoh
S
S
Department of Physiology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, 990-9585, Yamagata, Japan.
Ito
K
K
Fujii
S
S
Kaneko
K
K
Kato
K
K
Mikoshiba
K
K
Kato
H
H
D000818:Animals; D015220:Calcium Channels / Q000172:deficiency* / Q000235:genetics; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D053496:Inositol 1,4,5-Trisphosphate Receptors; D017774:Long-Term Potentiation / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout / Q000033:anatomy & histology / Q000235:genetics / Q000378:metabolism; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism* / Q000648:ultrastructure; D009473:Neuronal Plasticity; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000172:deficiency* / Q000235:genetics; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000235:genetics*
D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear