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

功能神经通路可视化的新型遗传策略的开发和应用

基本信息

批准号：
10558117
负责人：
YOSHIHARA Yoshihiro
金额：
$ 7.3万
依托单位：
RIKEN
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10558117/
关键词：
Wheat Germ Agglutinin Transsynaptic Tracer Neural Network Transgenic Mouse Adenovirus Olfactory Pathway Visual Pathway Cerebellar Efferent Pathway 視覚回路嗅覚系神経回路小脳遠心性神経回路

项目摘要

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.

神经元之间的信息传递发生在突触。通过特定的突触连接之间的各种神经元之间的接线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知识对于理解广泛的大脑功能至关重要。我们通过将神经解剖学方法与转基因和基因靶向技术相结合，开发了一种强大的遗传策略，用于可视化突触的特定神经元途径。通过在特定启动子元素的控制下引入植物凝集素，小麦胚芽凝集素（WGA）的cDNA，作为转基因，可以看到选择性和功能性的经突触神经途径。 L7启动子用于在小脑Purkinje细胞中特异性表达。在L7-WGA转基因小鼠中，小脑传出途径（从Purkinje细胞到深小脑核，再到丘脑腹侧外侧核和中脑红色核）。以类似的方式，使用WGA转基因方法标记嗅觉途径和视觉途径。此外，我们成功地开发了表达WGA的重组腺病毒。因此，该策略应极大地促进发展发展和成熟神经系统的解剖学和功能组织。