Fox Megan E, Mikhailova Maria A, Bass Caroline E, Takmakov Pavel, Gainetdinov Raul R, Budygin Evgeny A, Wightman R Mark
Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; UNC Neuroscience Center, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599;
Institute of Translational Biomedicine, St. Petersburg State University, St. Petersburg 199034, Russia;
Proc Natl Acad Sci U S A. 2016 Jun 21;113(25):6985-90. doi: 10.1073/pnas.1603629113. Epub 2016 Jun 13.
Dopamine signaling occurs on a subsecond timescale, and its dysregulation is implicated in pathologies ranging from drug addiction to Parkinson's disease. Anatomic evidence suggests that some dopamine neurons have cross-hemispheric projections, but the significance of these projections is unknown. Here we report unprecedented interhemispheric communication in the midbrain dopamine system of awake and anesthetized rats. In the anesthetized rats, optogenetic and electrical stimulation of dopamine cells elicited physiologically relevant dopamine release in the contralateral striatum. Contralateral release differed between the dorsal and ventral striatum owing to differential regulation by D2-like receptors. In the freely moving animals, simultaneous bilateral measurements revealed that dopamine release synchronizes between hemispheres and intact, contralateral projections can release dopamine in the midbrain of 6-hydroxydopamine-lesioned rats. These experiments are the first, to our knowledge, to show cross-hemispheric synchronicity in dopamine signaling and support a functional role for contralateral projections. In addition, our data reveal that psychostimulants, such as amphetamine, promote the coupling of dopamine transients between hemispheres.
多巴胺信号传导发生在亚秒级时间尺度上,其失调与从药物成瘾到帕金森病等多种病理状况有关。解剖学证据表明,一些多巴胺神经元具有跨半球投射,但这些投射的意义尚不清楚。在此,我们报告了在清醒和麻醉大鼠的中脑多巴胺系统中前所未有的半球间通信。在麻醉大鼠中,对多巴胺细胞进行光遗传学和电刺激可在对侧纹状体中引发与生理相关的多巴胺释放。由于D2样受体的差异调节,背侧和腹侧纹状体的对侧释放有所不同。在自由活动的动物中,同步双侧测量显示,半球间多巴胺释放同步,完整的对侧投射可在6-羟基多巴胺损伤大鼠的中脑中释放多巴胺。据我们所知,这些实验首次表明多巴胺信号传导存在跨半球同步性,并支持对侧投射的功能作用。此外,我们的数据表明,精神兴奋剂,如苯丙胺,可促进半球间多巴胺瞬变的耦合。
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