The neuronal nicotinic acetylcholine receptors α4* and α6* differentially modulate dopamine release in mouse striatal slices
The neuronal nicotinic acetylcholine receptors α4* and α6* differentially modulate dopamine release in mouse striatal slices
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DOI：
10.1111/j.1471-4159.2008.05266.x
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发表时间：
2008-06-01
影响因子：
4.7
通讯作者：
McIntosh, J. Michael
中科院分区：
文献类型：
--
作者：
Meyer, Erin L.;Yoshikami, Doju;McIntosh, J. Michael
纹状体多巴胺（DA）在运动协调的调节和显着信息的处理中发挥着重要作用。我们使用伏安法监测纹状体切片中电刺激引起的 DA 释放，其中中间神经元不断释放乙酰胆碱。使用 α 6 选择性拮抗剂 α 芋螺毒素 MII[E11A] 和 α 4 敲除小鼠能够鉴定出两个 DA 能纤维群体。第一个群体的动作电位阈值较低，这些纤维的动作电位诱发的 DA 释放受到 α 6 的调节。第二个群体的动作电位阈值较高，并且只有 α 4（非 α 6）调节动作电位诱发的 DA 释放。纹状体 DA 能神经元以强直和阶段性模式放电。当在火车中施加刺激来模拟阶段性放电时，与野生型小鼠相比，α4 敲除小鼠观察到更多的 DA 释放。此外，阻断α 4（非α 6），但不阻断α 6，会增加火车引起的DA释放。这些结果表明存在不同类别的纹状体 DA 能纤维表达不同的烟碱受体亚型。
Striatal dopamine (DA) plays a major role in the regulation of motor coordination and in the processing of salient information. We used voltammetry to monitor DA-release evoked by electrical stimulation in striatal slices, where interneurons continuously release acetylcholine. Use of the alpha 6-selective antagonist alpha-conotoxin MII[E11A] and alpha 4 knockout mice enabled identification of two populations of DA-ergic fibers. The first population had a low action potential threshold, and action potential-evoked DA-release from these fibers was modulated by alpha 6. The second population had a higher action potential threshold, and only alpha 4(non-alpha 6) modulated action potential-evoked DA-release. Striatal DA-ergic neurons fire in both tonic and phasic patterns. When stimuli were applied in a train to mimic phasic firing, more DA-release was observed in alpha 4 knockout versus wild-type mice. Furthermore, block of alpha 4(non-alpha 6), but not of alpha 6, increased DA release evoked by a train. These results indicate that there are different classes of striatal DA-ergic fibers that express different subtypes of nicotinic receptors.