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。通过特定突触连接的不同类型神经元之间的连接模式是大脑用于信息处理的功能逻辑的基础。因此，对神经元网络的详细了解对于理解广泛的大脑功能是必不可少的。通过将神经解剖学追踪方法与转基因和基因打靶技术相结合，我们开发了一种强大的遗传策略，用于显示穿过突触的特定神经元路径。通过引入植物凝集素基因，小麦胚芽凝集素(WGA)作为特定启动子元件控制下的转基因，可以显示选择性和功能性的跨突触神经通路。利用L7启动子在小脑浦肯野细胞中特异性表达WGA。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。用WGA转基因方法标记嗅觉通路和视觉通路。此外，我们还成功地研制了表达WGA的重组腺病毒。因此，这一策略应该会极大地促进对发育和成熟神经系统的解剖学和功能组织的研究。

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.