G(alpha)q-deficient mice lack metabotropic glutamate receptor-dependent long-term depression but show normal long-term potentiation in the hippocampal CA1 region.
Long-term potentiation (LTP) and depression (LTD) are potential cellular mechanisms involved in learning and memory. Group I metabotropic glutamate receptors (mGluR), which are linked to heterotrimeric G-proteins of the G(q) family (G(q) and G(11)), have been reported to facilitate both hippocampal LTP and LTD. To evaluate their functional role in synaptic plasticity, we studied LTD and LTP in the CA1 region of the hippocampus from wild-type, Galpha(q)(-/-), and Galpha(11)(-/-) mice. Basic parameters of the synaptic transmission were not altered in Galpha(q)(-/-) and Galpha(11)(-/-) mice. Moreover, these mice showed normal LTP in response to a strong tetanus and to a weak tetanus. However, LTD induced either by a group I mGluRs agonist or by paired-pulse low-frequency stimulation (PP-LFS) was absent in Galpha(q)(-/-) mice. Moreover, PP-LFS caused potentiation of the synaptic transmission in these mice that was not affected by the NMDAR antagonist AP-5. These results show that G(q) plays a crucial role in the mGluR-dependent LTD, whereas hippocampal LTP is not affected by the lack of a single member of the G(q) family.
Kleppisch
T
T
Institut für Pharmakologie und Toxikologie, Technische Universität München, 80802 München, Germany. kleppisch@ipt.med.tu-muenchen.de
Voigt
V
V
Allmann
R
R
Offermanns
S
S
D000818:Animals; D003433:Crosses, Genetic; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020962:Heterotrimeric GTP-Binding Proteins