Schotanus Sietske M, Chergui Karima
Department of Physiology and Pharmacology, Section of Molecular Neurophysiology, The Karolinska Institute, Stockholm, Sweden.
J Neurochem. 2008 Aug;106(4):1758-65. doi: 10.1111/j.1471-4159.2008.05512.x. Epub 2008 Jun 7.
NMDA receptors play essential roles in the physiology and pathophysiology of the striatum, a brain nucleus involved in motor control and reward-motivated behaviors. NMDA receptors are composed of NR1 and NR2A-D subunits. Functional properties of NMDA receptors are determined by the type of NR2 subunit they contain. In this study, we have examined the involvement of NR2B and NR2A in the modulatory effect of NMDA on glutamatergic and dopaminergic synaptic transmission in the striatum. We found that bath application of NMDA decreased the amplitude of the field excitatory post-synaptic potential/population spike (fEPSP/PS) measured in corticostriatal mouse brain slices. This depression was not affected by the NR2B-selective antagonists Ifenprodil and Ro 25-6981, but was abolished by the NR2A antagonist NVP-AAM077. Activation of corticostriatal neurons by NMDA did not contribute to synaptic depression because similar results were obtained in decorticated striatal slices. Synaptic depression was not dependent on GABA release because the GABA(A) receptor antagonist bicuculline did not affect NMDA-induced decrease of the fEPSP/PS. NMDA also depressed evoked-dopamine release through NR2A- but not NR2B-containing NMDA receptors. Our results identify an important role for NR2A-containing NMDA receptors intrinsic to the striatum in regulating glutamatergic synaptic transmission and evoked-dopamine release.
N-甲基-D-天冬氨酸（NMDA）受体在纹状体的生理和病理生理过程中发挥着重要作用，纹状体是一个参与运动控制和奖赏驱动行为的脑核。NMDA受体由NR1和NR2A-D亚基组成。NMDA受体的功能特性由其所含NR2亚基的类型决定。在本研究中，我们检测了NR2B和NR2A在NMDA对纹状体中谷氨酸能和多巴胺能突触传递的调节作用中的参与情况。我们发现，在皮质纹状体小鼠脑片中，浴加NMDA可降低所测的场兴奋性突触后电位/群体峰电位（fEPSP/PS）的幅度。这种抑制不受NR2B选择性拮抗剂艾芬地尔和Ro 25-6981的影响，但被NR2A拮抗剂NVP-AAM077消除。NMDA对皮质纹状体神经元的激活并非导致突触抑制的原因，因为在去皮质纹状体切片中也获得了类似结果。突触抑制不依赖于γ-氨基丁酸（GABA）的释放，因为GABA（A）受体拮抗剂荷包牡丹碱并不影响NMDA诱导的fEPSP/PS降低。NMDA还通过含NR2A而非含NR2B的NMDA受体抑制诱发的多巴胺释放。我们的结果表明，纹状体内含NR2A的NMDA受体在调节谷氨酸能突触传递和诱发的多巴胺释放中起着重要作用。
