title: Regulation of dopamine D2 receptor-mediated extracellular signal-regulated kinase signaling and spine formation by GABAA receptors in hippocampal neurons.
abstract: Dopamine (DA) signaling via DA receptors is known to control hippocampal activity that contributes to learning, memory, and synaptic plasticity. In primary hippocampal neuronal culture, we observed that dopamine D2 receptors (D2R) co-localized with certain subtypes of GABAA receptors, namely α1, β3, and γ2 subunits, as revealed by double immunofluorocytochemical analysis. Treatment with the D2R agonist, quinpirole, was shown to elicit an increase in phosphorylation of extracellular signal-regulated kinase (ERK) in hippocampal neurons. This phosphorylation was inhibited by pretreatment with the GABAA receptor agonist, muscimol. Furthermore, treatment of hippocampal neurons with quinpirole increased the dendritic spine density and this regulation was totally blocked by pretreatment with a MAP kinase kinase (MEK) inhibitor (PD98059), D2R antagonist (haloperidol), or by the GABAA receptor agonist, muscimol. These results suggest that D2R-mediated ERK phosphorylation can control spine formation and that the GABAA receptor negatively regulates the D2R-induced spine formation through ERK signaling in hippocampal neurons, thus indicating a potential role of D2R in the control of hippocampal neuronal excitability.
authors.affiliation: Molecular Neurobiology Laboratory, Department of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, South Korea.
authors.forename: Dong-Hoon
authors.initials: DH
authors.lastname: Yoon
authors.affiliation: Molecular Neurobiology Laboratory, Department of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, South Korea.
authors.forename: Sehyoun
authors.initials: S
authors.lastname: Yoon
authors.affiliation: Molecular Neurobiology Laboratory, Department of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, South Korea.
authors.forename: Donghoon
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Anatomy, College of Medicine, Korea University, Brain Korea 21, Seoul 136-705, South Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Molecular Neurobiology Laboratory, Department of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul 136-701, South Korea. Electronic address: jahyunb@korea.ac.kr.
authors.forename: Ja-Hyun
authors.initials: JH
authors.lastname: Baik
mesh_terms: D000818:Animals; D049229:Dendritic Spines / Q000502:physiology; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure; D020935:MAP Kinase Signaling System; D008813:Mice, Inbred ICR; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D061251:Primary Cell Culture; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D017448:Receptors, Dopamine D2; D011963:Receptors, GABA-A; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Dendritic spine; Dopamine; ERK; GABA; Hippocampal neurons