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The Journal of Neuroscience, October 1, 2002, 22(19):8379-8390

Group I Metabotropic Glutamate Receptor Signaling via Galpha q/Galpha 11 Secures the Induction of Long-Term Potentiation in the Hippocampal Area CA1

Masami Miura1, Masahiko Watanabe2, Stefan Offermanns3, Melvin I. Simon4, and Masanobu Kano1

1 Department of Physiology, Kanazawa University School of Medicine, Takara-machi, Kanazawa 920-8640, Japan, 2 Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8635, Japan, 3 Pharmakologisches Institut, Abteilung Molekulare Pharmakologie, Universität Heidelberg, 69120 Heidelberg, Germany, and 4 Division of Biology, California Institute of Technology, Pasadena, California 91125

Heterotromeric G-proteins of the Gq family are thought to transduce signals from group I metabotropic glutamate receptors (mGluRs) in central neurons. We investigated roles of this cascade in hippocampal long-term potentiation (LTP) by using null-mutant mice lacking the alpha  subunit of Gq (Galpha q) or G11 (Galpha 11). We found no obvious abnormalities in the morphology, layer structure, expression of NMDA receptors, and basic parameters of excitatory synaptic transmission in the hippocampus of Galpha q mutant mice. We used theta burst stimulation (TBS) (3-10 burst trains at 5 Hz; each train consisted of five stimuli at 100 Hz) to induce LTP at Schaffer collateral to CA1 pyramidal cell synapses. Conventional TBS with 10 burst trains induced robust LTP in wild-type, Galpha q mutant, and Galpha 11 mutant mice. Weak TBS with three burst trains consistently induced LTP in wild-type mice. In contrast, the same weak TBS was insufficient to induce LTP in Galpha q and Galpha 11 mutant mice. In wild-type mice, the LTP by weak TBS was abolished by inhibiting group I mGluR or protein kinase C (PKC) but not by blocking muscarinic acetylcholine receptors. Prior activation of group I mGluR by an agonist significantly enhanced the LTP by weak TBS in wild-type mice. However, this priming effect was absent in Galpha q mutant mice. These results indicate that the signaling from group I mGluR to PKC involving Galpha q/Galpha 11 does not constitute the main pathway for LTP, but it secures LTP induction by lowering its threshold in the hippocampal area CA1.

Key words: long-term potentiation; hippocampus; metabotropic glutamate receptor; G-protein; protein kinase C; mouse


Copyright © 2002 Society for Neuroscience  0270-6474/02/22198379-12$05.00/0


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