Dopamine modulation of excitatory currents in the striatum is dictated by the expression of D1 or D2 receptors and modified by endocannabinoids
Dopamine modulation of excitatory currents in the striatum is dictated by the expression of D1 or D2 receptors and modified by endocannabinoids
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DOI：
10.1111/j.1460-9568.2009.07047.x
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发表时间：
2010-01-01
影响因子：
3.4
通讯作者：
Levine, Michael S.
中科院分区：
文献类型：
--
作者：
Andre, Veronique M.;Cepeda, Carlos;Levine, Michael S.
纹状体中等棘神经元（mssn）接受突触前和突触后多巴胺调节的谷氨酸能输入。利用表达增强绿色荧光蛋白基因作为报告基因的小鼠，鉴定含有D1或D2受体亚型的mssn，检测多巴胺对切片中自发兴奋性突触后电流（sEPSCs）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）电流的调节。结果显示多巴胺受体特异性调节sEPSCs。多巴胺和D1激动剂增加了表达D1受体的mssn （D1细胞）中sEPSC的频率，而多巴胺和D2激动剂降低了表达D2受体的mssn （D2细胞）中sEPSC的频率。这些作用完全（D1细胞）或部分（D2细胞）通过内源性大麻素逆行信号介导。大麻素1受体（CB1R）激动剂和anandamide转运体阻滞剂阻止D1受体介导的D1细胞sEPSC频率的增加，而CB1R拮抗剂部分阻断D2细胞sEPSC频率的降低。在突触后水平，低浓度的D1受体激动剂在急性分离的D1细胞中持续增加NMDA和AMPA电流，而D2受体激动剂在急性分离的D2细胞中降低这些电流。这些结果表明，谷氨酸释放和突触后兴奋电流在相反的方向上受到D1或D2受体激活的调节。这种调控的方向也是D1和D2细胞所特有的。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CB1Rs，从而在谷氨酸末端投射到D1和D2细胞中不同地调节谷氨酸释放。
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.