Department of Cellular Neurobiology Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, 113-0033 Japan.
Department of Experimental Psychology, University College London, 26 Bedford Way, WC1H 0AP, London, UK.
eNeuro. 2018 Feb 6;5(1). doi: 10.1523/ENEURO.0071-17.2018. eCollection 2018 Jan-Feb.
Catecholaminergic (dopamine and norepinephrine) projections to the cortex play an important role in cognitive functions and dysfunctions including learning, addiction, and mental disorders. While dynamics of glutamatergic synapses have been well studied in such contexts, little is known regarding catecholaminergic projections, owing to lack of robust methods. Here we report a system to monitor catecholaminergic projections over the timeframes that such events occur. Green fluorescent protein (GFP) expression driven by tyrosine hydroxylase promoter in a transgenic mouse line enabled us to perform two-photon imaging of cortical catecholaminergic projections through a cranial window. Repetitive imaging of the same axons over 24 h revealed the highly dynamic nature of catecholaminergic boutons. Surprisingly, administration of single high dose methamphetamine (MAP) induced a transient increase in bouton volumes. This new method opens avenues for longitudinal evaluation of structural changes at single release sites of catecholamines in association with physiology and pathology of cortical functions.
儿茶酚胺（多巴胺和去甲肾上腺素）投射到皮层在认知功能和功能障碍中发挥重要作用，包括学习、成瘾和精神障碍。虽然谷氨酸能突触的动力学在这些情况下已经得到了很好的研究，但由于缺乏强有力的方法，对于儿茶酚胺投射知之甚少。在这里，我们报告了一种系统，可以在这些事件发生的时间范围内监测儿茶酚胺投射。在转基因小鼠系中，酪氨酸羟化酶启动子驱动的绿色荧光蛋白（GFP）表达使我们能够通过颅窗进行皮质儿茶酚胺投射的双光子成像。在 24 小时内对同一轴突进行重复成像，揭示了儿茶酚胺末梢的高度动态性质。令人惊讶的是，单次高剂量甲基苯丙胺（MAP）的给药会导致末梢体积短暂增加。这种新方法为纵向评估儿茶酚胺在单个释放部位的结构变化开辟了道路，与皮质功能的生理学和病理学有关。
