Mental Retardation Research Center, David Geffen School of Medicine at UCLA, Semel Institute for Neuroscience and Human Behavior, 760 Westwood Plaza, NPI 58-258, Los Angeles, CA 90095, USA.
Eur J Neurosci. 2010 Jan;31(1):14-28. doi: 10.1111/j.1460-9568.2009.07047.x. Epub 2009 Dec 21.
Striatal medium-sized spiny neurons (MSSNs) receive glutamatergic inputs modulated presynaptically and postsynaptically by dopamine. Mice expressing the gene for enhanced green fluorescent protein as a reporter gene to identify MSSNs containing D1 or D2 receptor subtypes were used to examine dopamine modulation of spontaneous excitatory postsynaptic currents (sEPSCs) in slices and postsynaptic N-methyl-d-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) currents in acutely isolated cells. The results demonstrated dopamine receptor-specific modulation of sEPSCs. Dopamine and D1 agonists increased sEPSC frequency in D1 receptor-expressing MSSNs (D1 cells), whereas dopamine and D2 agonists decreased sEPSC frequency in D2 receptor-expressing MSSNs (D2 cells). These effects were fully (D1 cells) or partially (D2 cells) mediated through retrograde signaling via endocannabinoids. A cannabinoid 1 receptor (CB1R) agonist and a blocker of anandamide transporter prevented the D1 receptor-mediated increase in sEPSC frequency in D1 cells, whereas a CB1R antagonist partially blocked the decrease in sEPSC frequency in D2 cells. At the postsynaptic level, low concentrations of a D1 receptor agonist consistently increased NMDA and AMPA currents in acutely isolated D1 cells, whereas a D2 receptor agonist decreased these currents in acutely isolated D2 cells. These results show that both glutamate release and postsynaptic excitatory currents are regulated in opposite directions by activation of D1 or D2 receptors. The direction of this regulation is also specific to D1 and D2 cells. We suggest that activation of postsynaptic dopamine receptors controls endocannabinoid mobilization, acting on presynaptic CB1Rs, thus modulating glutamate release differently in glutamate terminals projecting to D1 and D2 cells.
纹状体中型棘突神经元 (MSSNs) 接收谷氨酸能输入，这些输入在突触前和突触后受到多巴胺的调制。使用表达增强型绿色荧光蛋白作为报告基因以识别含有 D1 或 D2 受体亚型的 MSSNs 的基因工程小鼠，来检查多巴胺对切片中自发兴奋性突触后电流 (sEPSC) 和急性分离细胞中突触后 N-甲基-D-天冬氨酸 (NMDA) 和 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸 (AMPA) 电流的调制作用。结果表明多巴胺受体对 sEPSC 具有特异性调制作用。多巴胺和 D1 激动剂增加了 D1 受体表达的 MSSNs (D1 细胞) 中的 sEPSC 频率，而多巴胺和 D2 激动剂降低了 D2 受体表达的 MSSNs (D2 细胞) 中的 sEPSC 频率。这些作用完全 (D1 细胞) 或部分 (D2 细胞) 通过内源性大麻素的逆行信号转导介导。大麻素 1 型受体 (CB1R) 激动剂和 anandamide 转运体的阻断剂可防止 D1 受体介导的 D1 细胞中 sEPSC 频率的增加，而 CB1R 拮抗剂部分阻断了 D2 细胞中 sEPSC 频率的降低。在突触后水平，低浓度的 D1 受体激动剂一致增加了急性分离的 D1 细胞中的 NMDA 和 AMPA 电流，而 D2 受体激动剂降低了急性分离的 D2 细胞中的这些电流。这些结果表明，D1 或 D2 受体的激活均以相反的方向调节谷氨酸释放和突触后兴奋性电流。这种调节的方向也对 D1 和 D2 细胞具有特异性。我们认为，突触后多巴胺受体的激活控制内源性大麻素的动员，作用于突触前 CB1R，从而以不同的方式调节投射到 D1 和 D2 细胞的谷氨酸能末梢中的谷氨酸释放。
