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

• Published in: Brain research Vol. 901; no. 1; pp. 237 - 246
• Main Authors: Itoh, Satoshi, Ito, Ken-Ichi, Fujii, Satoshi, Kaneko, Kenya, Kato, Kunio, Mikoshiba, Katsuhiko, Kato, Hiroshi
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 18-05-2001; Amsterdam Elsevier; New York, NY
• Subjects: Animals; Biological and medical sciences; Calcium Channels - deficiency; Calcium Channels - genetics; Central nervous system; Depotentiation; Electric Stimulation; Electrophysiology; Excitatory Postsynaptic Potentials - genetics; Fundamental and applied biological sciences. Psychology; Inositol 1,4,5-Trisphosphate Receptors; Long-term depression; Long-term potentiation; Long-Term Potentiation - genetics; mGluR1; Mice; Mice, Knockout - anatomy & histology; Mice, Knockout - genetics; Mice, Knockout - metabolism; Mossy Fibers, Hippocampal - metabolism; Mossy Fibers, Hippocampal - ultrastructure; Neuronal Plasticity; Neurons - cytology; Neurons - metabolism; NMDA receptor; Receptors, Cytoplasmic and Nuclear - deficiency; Receptors, Cytoplasmic and Nuclear - genetics; Synapses - metabolism; Synapses - ultrastructure; Synaptic Transmission - genetics; Vertebrates: nervous system and sense organs; Depotentiation; mGluR1; Excitable membranes and synaptic transmission; NMDA receptor; Long-term depression; Long-term potentiation; Potentiation; Mossy fiber; Targeting; Rodentia; Central nervous system; Inositol phosphate; Long term; Vertebrata; Synapse; Mammalia; Gene; Mouse; Synaptic transmission; Plasticity; Mutation; Hippocampus; Brain (vertebrata); Biological receptor
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(01)02373-3

In the present study, we used inositol-1,4,5-trisphosphate (IP
3) type 1 receptor (IP
3R1) 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 (IP
3R1
+/+) and IP
3R1 knockout mice (IP
3R1
−/−), showing that basic synaptic transmission does not involve IP
3R1 activation. Tetanus induced LTP in both wild-type and IP
3R1
−/− mice, but the magnitude of LTP was significantly greater in IP
3R1
−/− 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 IP
3R1 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 μM); under these conditions, the LTP in both IP
3R1
−/− and IP
3R1
+/+ 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 IP
3R1
−/− (117.6±1.7%,
n=8) and IP
3R1
+/+ (116.9±1.8%,
n=5) mice. The IP
3R1 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 IP
3R1
−/− and wild-type mice.