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

外源性和非侵入性控制神经元活动的光学方法允许对神经回路和突触传输进行详细分析。我们利用通道视紫红质-2和卤视紫红质，在动物模型线虫秀丽线虫中建立了“光遗传学”，以双向控制神经元膜电位，并在活动物中触发、抑制或干扰由各自细胞调节的行为。这种方法的成功促使我们有兴趣改进现有的工具，寻找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。我们将在线虫的不同神经元中实施这种由For成员研究和/或产生的“光开关”。这包括光激活的腺苷环化酶(PAC)、鸟苷环化酶(待开发)、通道视紫红质变体和其他视紫红质(细菌视紫红质、蛋白视紫红质)，其颜色变体可供选择。此外，我们将实现光激活的谷氨酸受体LiGluR，并产生光激活的乙酰胆碱受体(LiAChR)。将这些工具引入线虫不同的感觉神经元或中间神经元，我们将研究感觉感觉习惯化的机制，无论是在感觉细胞内，在它们的输出突触上，还是在下游的中间神经元上。

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.