Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA.
Mol Brain. 2010 Jun 22;3:20. doi: 10.1186/1756-6606-3-20.
Interactions between dopamine and glutamate in the prefrontal cortex are essential for cognitive functions such as working memory. Modulation of N-methyl-D-aspartic acid (NMDA) receptor functions by dopamine D1 receptor is believed to play a critical role in these functions. The aim of the work reported here is to explore the signaling pathway underlying D1 receptor-mediated trafficking of NMDA receptors in cultured rat prefrontal cortical neurons.
Activation of D1 receptor by selective agonist SKF-81297 significantly increased the expression of NR2B subunits. This effect was completely blocked by small interfering RNA knockdown of Fyn, but not Src. Under control conditions, neither Fyn nor Src knockdown exhibited significant effect on basal NR2B expression. D1 stimulation significantly enhanced NR2B insertion into plasma membrane in cultured PFC neurons, a process obstructed by Fyn, but not Src, knockdown.
Dopamine D1 receptor-mediated increase of NMDA receptors is thus Fyn kinase dependent. Targeting this signaling pathway may be useful in treating drug addiction and schizophrenia.
前额叶皮层中多巴胺和谷氨酸之间的相互作用对于工作记忆等认知功能至关重要。多巴胺 D1 受体对 N-甲基-D-天冬氨酸（NMDA）受体功能的调节被认为在这些功能中起着关键作用。本研究旨在探讨多巴胺 D1 受体介导的培养的大鼠前额叶皮质神经元中 NMDA 受体转运的信号通路。
选择性激动剂 SKF-81297 激活 D1 受体可显著增加 NR2B 亚基的表达。该作用可被 Fyn 的小干扰 RNA 敲低完全阻断，但Src 的小干扰 RNA 敲低则不能阻断。在对照条件下，Fyn 或 Src 的敲低均对基础 NR2B 表达无显著影响。D1 刺激可显著增强培养的 PFC 神经元中 NMDA 受体向质膜的插入，该过程可被 Fyn 而非 Src 敲低所阻断。
多巴胺 D1 受体介导的 NMDA 受体增加是 Fyn 激酶依赖性的。靶向该信号通路可能对治疗药物成瘾和精神分裂症有用。
