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The Journal of Neuroscience, October 1, 2002, 22(19):8379-8390
Group I Metabotropic Glutamate Receptor Signaling via
G q/G11 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  subunit of Gq (Gq) or G11 (G11). 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 Gq 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, Gq mutant, and G11 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 Gq and G11
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 Gq mutant mice. These results indicate that the signaling from group I mGluR to PKC
involving Gq/G11 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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