Re-engineering Rabies Virus

项目摘要 大脑的每一部分都是由许多不同类型的神经元紧密相连组成的， 每个在电路中扮演着完全不同的角色。狂犬病病毒载体已成为不可或缺的工具， 揭示了这种通常难以辨认的混乱的组织，因为它们允许识别 神经元的突触连接网络。它们还允许监控和操纵 通过光遗传学和其他技术检测病毒标记神经元的活性， 可以揭示神经回路的识别组件的心理过程。尽管它们很有用， 然而，狂犬病病毒载体也有缺点，其中主要的缺点是它们对标记的神经元的毒性， 阻止了它们在长期的生理和行为实验中的使用，这些实验将为以下方面提供重要的见解： 认知的生物学基础在本项目中，我们将开发新一代狂犬病病毒载体， 单突触追踪系统的基础上，他们将允许完全无毒的荧光标记，光学 监测和突触连接的神经元网络的光遗传学操纵。

PROJECT SUMMARY Every part of the brain is composed of dense tangles of heavily-interconnected neurons of many different types, each playing completely different roles in the circuitry. Rabies viral vectors have become indispensable tools for revealing the organization of this otherwise generally indecipherable jumble, because they allow the identification of synaptically-connected networks of neurons within the tissue. They also allow monitoring and manipulation of the activity of the virally-labeled neurons by optogenetics and other techniques, so that the contributions to mental processes of identified components of neural circuitry can be revealed. Despite their usefulness, however, rabies viral vectors have drawbacks, chief among which is their toxicity to the labeled neurons, which prevents their use in longer-term physiological and behavioral experiments that would provide major insights into the biological bases of cognition. In this project, we will develop a new generation of rabies viral vectors and monosynaptic tracing systems based on them that will allow completely nontoxic fluorescent labeling, optical monitoring, and optogenetic manipulation of synaptically-connected neuronal networks.