title: Costimulation of AMPA and metabotropic glutamate receptors underlies phospholipase C activation by glutamate in hippocampus.
abstract: Glutamate, a major neurotransmitter in the brain, activates ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs, respectively). The two types of glutamate receptors interact with each other, as exemplified by the modulation of iGluRs by mGluRs. However, the other way of interaction (i.e., modulation of mGluRs by iGluRs) has not received much attention. In this study, we found that group I mGluR-specific agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) alone is not sufficient to activate phospholipase C (PLC) in rat hippocampus, while glutamate robustly activates PLC. These results suggested that additional mechanisms provided by iGluRs are involved in group I mGluR-mediated PLC activation. A series of experiments demonstrated that glutamate-induced PLC activation is mediated by mGluR5 and is facilitated by local Ca(2+) signals that are induced by AMPA-mediated depolarization and L-type Ca(2+) channel activation. Finally, we found that PLC and L-type Ca(2+) channels are involved in hippocampal mGluR-dependent long-term depression (mGluR-LTD) induced by paired-pulse low-frequency stimulation, but not in DHPG-induced chemical LTD. Together, we propose that AMPA receptors initiate Ca(2+) influx via the L-type Ca(2+) channels that facilitate mGluR5-PLC signaling cascades, which underlie mGluR-LTD in rat hippocampus.
authors.affiliation: Department of Physiology and bioMembrane Plasticity Research Center, Seoul National University College of Medicine, Seoul 110-799, Korea, and.
authors.forename: Hye-Hyun
authors.initials: HH
authors.lastname: Kim
authors.affiliation: Department of Physiology and bioMembrane Plasticity Research Center, Seoul National University College of Medicine, Seoul 110-799, Korea, and.
authors.forename: Kyu-Hee
authors.identifier: http://orcid.org/0000-0001-7835-2645
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Department of Physiology and.
authors.forename: Doyun
authors.initials: D
authors.lastname: Lee
authors.affiliation: Department of Physiology and bioMembrane Plasticity Research Center, Seoul National University College of Medicine, Seoul 110-799, Korea, and.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Han
authors.affiliation: Department of Physiology and bioMembrane Plasticity Research Center, Seoul National University College of Medicine, Seoul 110-799, Korea, and.
authors.forename: Suk-Ho
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea jwsohn@kaist.ac.kr wonkyung@snu.ac.kr.
authors.forename: Jong-Woo
authors.initials: JW
authors.lastname: Sohn
authors.affiliation: Department of Physiology and bioMembrane Plasticity Research Center, Seoul National University College of Medicine, Seoul 110-799, Korea, and jwsohn@kaist.ac.kr wonkyung@snu.ac.kr.
authors.forename: Won-Kyung
authors.initials: WK
authors.lastname: Ho
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects; D018698:Glutamic Acid / Q000494:pharmacology / Q000502:physiology*; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism* / Q000502:physiology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology; D008297:Male; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5 / Q000819:agonists / Q000502:physiology*; D018091:Receptors, AMPA / Q000819:agonists* / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000378:metabolism; D012118:Resorcinols / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D020746:Calcium Channels, L-Type; C578937:Grm5 protein, rat; D064529:Receptor, Metabotropic Glutamate 5; D018091:Receptors, AMPA; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; D018698:Glutamic Acid; C079215:3,5-dihydroxyphenylglycine; D010738:Type C Phospholipases; D002118:Calcium; D005998:Glycine
keywords: Cav1.2; Cav1.3; confocal imaging; electrophysiology; local calcium; mGluR-LTD