Wu Hao, Williams John, Nathans Jeremy
Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States.
Department of Molecular Biology and Genetics, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, United States Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, United States Department of Opthalmology, Johns Hopkins University School of Medicine, Baltimore, United States
Elife. 2014 May 7;3:e02444. doi: 10.7554/eLife.02444.
The basal forebrain cholinergic system modulates neuronal excitability and vascular tone throughout the cerebral cortex and hippocampus. This system is severely affected in Alzheimer's disease (AD), and drug treatment to enhance cholinergic signaling is widely used as symptomatic therapy in AD. Defining the full morphologies of individual basal forebrain cholinergic neurons has, until now, been technically beyond reach due to their large axon arbor sizes. Using genetically-directed sparse labeling, we have characterized the complete morphologies of basal forebrain cholinergic neurons in the mouse. Individual arbors were observed to span multiple cortical columns, and to have >1000 branch points and total axon lengths up to 50 cm. In an AD model, cholinergic axons were slowly lost and there was an accumulation of axon-derived material in discrete puncta. Calculations based on published morphometric data indicate that basal forebrain cholinergic neurons in humans have a mean axon length of ∼100 meters.DOI: http://dx.doi.org/10.7554/eLife.02444.001.
基底前脑胆碱能系统调节整个大脑皮层和海马体的神经元兴奋性及血管张力。该系统在阿尔茨海默病（AD）中受到严重影响，增强胆碱能信号的药物治疗被广泛用作AD的对症疗法。由于基底前脑胆碱能神经元的轴突分支较大，迄今为止，确定单个基底前脑胆碱能神经元的完整形态在技术上还无法实现。利用基因导向的稀疏标记，我们已描绘出小鼠基底前脑胆碱能神经元的完整形态。观察到单个分支跨越多个皮质柱，具有超过1000个分支点，轴突总长度可达50厘米。在一个AD模型中，胆碱能轴突逐渐丧失，并且在离散的小点中有轴突衍生物质的积累。根据已发表的形态测量数据进行的计算表明，人类基底前脑胆碱能神经元的平均轴突长度约为100米。DOI: http://dx.doi.org/10.7554/eLife.02444.001 。
