Wang Li, Zhang Xiaoyu, Xu Huadong, Zhou Li, Jiao Ruiying, Liu Wei, Zhu Feipeng, Kang Xinjiang, Liu Bin, Teng Sasa, Wu Qihui, Li Mingli, Dou Haiqiang, Zuo Panli, Wang Changhe, Wang Shirong, Zhou Zhuan
State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China.
State Key Laboratory of Biomembrane and Membrane Biotechnology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China
J Physiol. 2014 Aug 15;592(16):3559-76. doi: 10.1113/jphysiol.2014.271825. Epub 2014 Jun 27.
Striatal dopamine (DA) is critically involved in major brain functions such as motor control and deficits such as Parkinson's disease. DA is released following stimulation by two pathways: the nigrostriatal pathway and the cholinergic interneuron (ChI) pathway. The timing of synaptic transmission is critical in striatal circuits, because millisecond latency changes can reverse synaptic plasticity from long-term potentiation to long-term depression in a DA-dependent manner. Here, we determined the temporal components of ChI-driven DA release in striatal slices from optogenetic ChAT-ChR2-EYFP mice. After a light stimulus at room temperature, ChIs fired an action potential with a delay of 2.8 ms. The subsequent DA release mediated by nicotinic acetylcholine (ACh) receptors had a total latency of 17.8 ms, comprising 7.0 ms for cholinergic transmission and 10.8 ms for the downstream terminal DA release. Similar latencies of DA release were also found in striatal slices from wild-type mice. The latency of ChI-driven DA release was regulated by inhibiting the presynaptic vesicular ACh release. Moreover, we describe the time course of recovery of DA release via the two pathways and that of vesicle replenishment in DA terminals. Our work provides an example of unravelling the temporal building blocks during fundamental synaptic terminal-terminal transmission in motor regulation.
纹状体多巴胺（DA）在诸如运动控制等主要脑功能以及诸如帕金森病等功能缺陷中起着关键作用。DA 通过两条途径受刺激后释放：黑质纹状体途径和胆碱能中间神经元（ChI）途径。突触传递的时间在纹状体回路中至关重要，因为毫秒级的潜伏期变化可以以 DA 依赖的方式将突触可塑性从长期增强转变为长期抑制。在此，我们确定了来自光遗传学 ChAT-ChR2-EYFP 小鼠的纹状体切片中 ChI 驱动的 DA 释放的时间成分。在室温下进行光刺激后，ChI 产生动作电位的延迟为 2.8 毫秒。随后由烟碱型乙酰胆碱（ACh）受体介导的 DA 释放的总潜伏期为 17.8 毫秒，其中胆碱能传递为 7.0 毫秒，下游终末 DA 释放为 10.8 毫秒。在野生型小鼠的纹状体切片中也发现了类似的 DA 释放潜伏期。ChI 驱动的 DA 释放潜伏期通过抑制突触前囊泡 ACh 释放来调节。此外，我们描述了通过这两条途径的 DA 释放恢复的时间进程以及 DA 终末中囊泡补充的时间进程。我们的工作提供了一个在运动调节中基本突触终末 - 终末传递过程中解析时间组成部分的例子。
