Development and application of a novel genetic strategy for visualization of functional neural pathways

神经元之间的信息传递发生在突触上。通过特定突触连接的各种类型的神经元之间的布线模式是大脑用于信息处理的功能逻辑的基础。因此，神经元网络的详细知识对于理解广泛的大脑功能至关重要。我们已经开发出一种强大的遗传策略，通过将神经解剖学追踪方法与转基因和基因靶向技术相结合，来可视化跨突触的特定神经元通路。通过引入植物凝集素的cDNA，小麦胚芽凝集素（WGA），作为一个特定的启动子元件控制下的转基因，选择性和功能性的跨突触神经通路可以可视化。L7启动子用于WGA在小脑浦肯野细胞中的特异性表达。在L7-WGA转基因小鼠中，小脑传出通路（从浦肯野细胞到小脑深核，再到丘脑腹外侧核和中脑红核）清晰可见。以类似的方式，用WGA转基因方法标记嗅觉通路和视觉通路。此外，我们已经成功地开发了表达WGA的重组腺病毒。因此，这一策略将极大地促进对发育和成熟神经系统的解剖和功能组织的研究。

Information transfer between neurons takes place at the synapse. The wiring patterns among various types of neurons via specific synaptic connections are the basis of functional logic employed by the brain for information processing. Thus, detailed knowledge of neuronal networks is essential for understanding the wide range of brain functions. We have developed a powerful genetic strategy for visualization of specific neuronal pathways across a synapse by combining a neuroanatomical tracing method with transgenic and gene targeting technology. By introducing cDNA for a plant lectin, wheat germ agglutinin (WGA), as a transgene under the control of specific promoter elements, selective and functional transsynaptic neural pathways could be visualized. L7 promoter was used for the expression of WGA specifically in the cerebellar Purkinje cells. In the L7-WGA transgenic mice, the cerebellar efferent pathways (from the Purkinje cells to the deep cerebellar nuclei and further to the thalamic ventrolateral nucleus and the midbrain red nucleus) were clearly visualized. In a similar manner, the olfactory pathways and the visual pathways were labeled with the WGA transgene method. In addition, we have succeeded in the development of WGA-expressing recombinant adenovirus. Thus, this strategy should greatly facilitate studies on the anatomical and functional organization of the developing and mature nervous system.