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.
Neuroscience. 2013 Oct 10;250:743-54. doi: 10.1016/j.neuroscience.2013.07.038. Epub 2013 Jul 25.
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.
为了研究谷氨酸受体亚型和 GABA 在口面部功能中的作用,我们在缺失(a)GluN2A、B 或 D 受体和(b)GABA 合成酶 65kDa 同工型谷氨酸脱羧酶(GAD65)的突变小鼠中量化了六种自发和多巴胺 D1 样受体激动剂 [R/S]-3-甲基-6-氯-7,8-二羟基-1-[3-甲基-苯基]-2,3,4,5-四氢-1H-3-苯并氮杂卓(SKF 83959)诱导的口面部运动的个体形貌。在 GluN2A 突变体中,头部运动的习惯化被破坏,触须运动减少,整体运动增加;对 SKF 83959 的反应性没有改变。在 GluN2B 突变体中,垂直和水平颌运动以及切牙喋喋不休增加,整体运动减少;在 SKF 83959 的挑战下,头部和触须运动减少。在 GluN2D 突变体中,水平颌运动、切牙喋喋不休和触须运动增加,舌突出减少,整体运动无变化;在 SKF 83959 的挑战下,水平颌运动增加。在 GAD65 突变体中,垂直颌运动增加,运动习惯化中断;在 SKF 83959 的挑战下,垂直和水平颌运动以及切牙喋喋不休减少。对口面部运动的影响与对整体运动行为调节的影响不同。这些发现(a)表明 GluN2A、B 和 D 受体以及 GAD65 介导的 GABA 在调节口面部运动的个体形貌方面具有新的、不同的作用;(b)揭示了这些作用如何与 D1 样受体在这些运动的模式发生器和效应器中的作用不同和/或相互作用。