Calcineurin plays different roles in group II metabotropic glutamate receptor- and NMDA receptor-dependent long-term depression.
We investigated metabotropic glutamate receptor (mGluR)-dependent long-term depression (LTD) in hippocampal CA1 pyramidal neurons of 6- to 8-d-old [postnatal days 6-8 (P6-P8)] and 21- to 25-d-old (P21-P25) rats. In P6-P8 rats, induction of LTD depended on the activity of group II mGluRs. In P21-P25 rats, however, this LTD disappeared, and instead, NMDA receptor (NMDAR)-dependent LTD appeared. A bath containing a specific calcineurin (CaN) inhibitor restored the group II mGluR-dependent LTD in the neurons of the P21-P25 rats. Although postsynaptic injection of CaN inhibitors suppressed NMDAR-dependent LTD, it did not affect induction of group II mGluR-dependent LTD. These results demonstrate that CaN plays different roles in the induction of two forms of LTD: presynaptic CaN inhibits group II mGluR-dependent LTD, whereas postsynaptic CaN facilitates NMDAR-dependent LTD. These findings are the first demonstration in vitro of group II mGluR-dependent LTD that is negatively regulated by CaN via an age-dependent mechanism.
Li
Sheng-Tian
ST
Mikoshiba Calciosignal Net Project, Exploratory Research for Advanced Technology, Japan Science and Technology Corporation, Tokyo 113-0021, Japan.
Kato
Kunio
K
Tomizawa
Kazuhito
K
Matsushita
Masayuki
M
Moriwaki
Akiyoshi
A
Matsui
Hideki
H
Mikoshiba
Katsuhiko
K
D000818:Animals; D000831:Animals, Newborn; D019703:Calcineurin / Q000502:physiology*; D065095:Calcineurin Inhibitors; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development*; D007700:Kinetics; D008959:Models, Neurological; D009473:Neuronal Plasticity; D017729:Presynaptic Terminals / Q000502:physiology; D017966:Pyramidal Cells / Q000254:growth & development* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013569:Synapses / Q000502:physiology
D065095:Calcineurin Inhibitors; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C108822:metabotropic glutamate receptor 2; D019703:Calcineurin