title: Phenotypic characterization of orofacial movement topography in mutants with disruption of amino acid mechanisms: glutamate N2A/B/D [GluRε1/2/4] subtypes and the GABA synthesizing enzyme GAD65.
abstract: To investigate the role of glutamate receptor subtypes and GABA in orofacial function, six individual topographies of orofacial movement, both spontaneous and induced by the dopamine D1-like receptor agonist [R/S]-3-methyl-6-chloro-7,8-dihydroxy-1-[3-methyl-phenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF 83959), were quantified in mutant mice with deletion of (a) GluN2A, B or D receptors, and (b) the GABA synthesizing enzyme, 65-kD isoform of glutamate decarboxylase (GAD65). In GluN2A mutants, habituation of head movements was disrupted and vibrissae movements were reduced, with an overall increase in locomotion; responsivity to SKF 83959 was unaltered. In GluN2B mutants, vertical and horizontal jaw movements and incisor chattering were increased, with an overall decrease in locomotion; under challenge with SKF 83959, head and vibrissae movements were reduced. In GluN2D mutants, horizontal jaw movements, incisor chattering and vibrissae movements were increased, with reduced tongue protrusions and no overall change in locomotion; under challenge with SKF 83959, horizontal jaw movements were increased. In GAD65 mutants, vertical jaw movements were increased, with disruption to habituation of locomotion; under challenge with SKF 83959, vertical and horizontal jaw movements and incisor chattering were decreased. Effects on orofacial movements differed from their effects on regulation of overall locomotor behavior. These findings (a) indicate novel, differential roles for GluN2A, B and D receptors and for GAD65-mediated GABA in the regulation of individual topographies of orofacial movement and (b) reveal how these roles differ from and/or interact with the established role of D1-like receptors in pattern generators and effectors for such movements.
authors.affiliation: Advanced Research Institute for the Sciences and Humanities, Nihon University, Tokyo 102-8251, Japan; Department of Pharmacology and Dental Research Centre, Nihon University School of Dentistry, Tokyo 101-8310, Japan. Electronic address: tomiyama.katsunori@nihon-u.ac.jp.
authors.forename: K
authors.initials: K
authors.lastname: Tomiyama
authors.forename: R
authors.initials: R
authors.lastname: Kato
authors.forename: Y
authors.initials: Y
authors.lastname: Hara
authors.forename: M
authors.initials: M
authors.lastname: Kobayashi
authors.forename: M
authors.initials: M
authors.lastname: Mishina
authors.forename: Y
authors.initials: Y
authors.lastname: Yanagawa
authors.forename: A
authors.initials: A
authors.lastname: Kinsella
authors.forename: N
authors.initials: N
authors.lastname: Koshikawa
authors.forename: J L
authors.initials: JL
authors.lastname: Waddington
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000031:analogs & derivatives / Q000494:pharmacology; D000596:Amino Acids / Q000502:physiology*; D000818:Animals; D018491:Dopamine Agonists / Q000494:pharmacology; D005152:Facial Muscles / Q000502:physiology*; D005260:Female; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D009055:Mouth / Q000502:physiology*; D009068:Movement / Q000502:physiology*; D009154:Mutation / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000819:agonists; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D012727:Sex Characteristics; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000596:Amino Acids; D018491:Dopamine Agonists; D005968:Glutamate Decarboxylase; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; C549071:Grin2d protein, mouse; C121001:NR2B NMDA receptor; C080703:SK&F 83959; C401141:glutamate decarboxylase 2
keywords: ANCOVA; DA; GABA; GAD65; HD; HET; Huntington’s disease; KO; PD; Parkinson’s disease; S.E.M.; SKF 83959; V; WT; [R/S]-3-methyl-6-chloro-7,8-dihydroxy-1-[3-methyl-phenyl]-2,3,4,5-tetrahydro-1H-3-benzazepine; analysis of covariance; dopamine; dopamine D1 receptors; glutamate GluN2A-D receptors; glutamate decarboxylase; heterozygous; knockout; mutant mice; orofacial movements; standard error of the mean; vehicle; wild-type