Developing and implementing novel light-switches in the nervous system of the nematode

在线虫神经系统中开发和实施新型光开关

• 批准号: 164461882
• 负责人: Professor Dr. Alexander Gottschalk
• 金额: --
• 依托单位: Buchmann Institute for Molecular Life Sciences
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/164461882?language=en
• 关键词: Developing; implementing; novel; light; switches

Optical methods for exogenous and non-invasive control of neuronal activity allow detailed analyses of neural circuits and synaptic transmission. We established “optogenetics” in an animal model, the nematode Caenorhabditis elegans, using Channelrhodopsin-2 and Halorhodopsin, to control the membrane potential of neurons bidirectionally and to trigger, inhibit or perturb behaviours regulated by the respective cells, in live animals. The success of this approach prompts our interest to improve current tools and to find additional light-activated proteins and enzymes to control other cellular processes, not only in neurons. We will implement such “light-switches”, studied and/or generated by members of the FOR, in different C. elegans neurons. This includes photo-activated adenylate cyclase (PAC), a guanylate cyclase (to be developed), Channelrhodopsin variants and other rhodopsins (Bacteriorhodopsin, Proteorhodopsin), for which colour-variants are available. Additionally, we will implement the light-activated glutamate receptor, LiGluR, and generate a light-activated acetylcholine receptor (LiAChR). Introducing these tools into different sensory neurons or interneurons of C. elegans, we will study mechanisms of habituation of sensory perception, either within the sensory cells, at their output synapses, or in downstream interneurons.

用于神经元活动的外源性和非侵入性控制的光学方法允许对神经回路和突触传递进行详细分析。我们在动物模型中建立了“光遗传学”，线虫秀丽隐杆线虫，使用视紫红质-2和Halorhodopsin双向控制神经元的膜电位，并在活体动物中触发，抑制或干扰由相应细胞调节的行为。这种方法的成功促使我们有兴趣改进现有的工具，并找到更多的光激活蛋白质和酶来控制其他细胞过程，而不仅仅是神经元。我们将在不同的C语言中实现这种由FOR成员研究和/或产生的“灯开关”。线虫神经元这包括光活化腺苷酸环化酶（PAC），鸟苷酸环化酶（待开发），视紫红质变体和其他视紫红质（细菌视紫红质，前视紫红质），其颜色变体可用。此外，我们将实现光激活谷氨酸受体，LiGluR，并产生光激活乙酰胆碱受体（LiAChR）。将这些工具导入C.我们将研究感觉知觉的习惯化机制，无论是在感觉细胞内，在它们的输出突触，还是在下游的中间神经元。