Biogenic monoamines are relevant to influential psychological diseases and brain plasicity. Knowledge obtained so far is however not enough for both of scientific and medical purposes. One obstacle against proceeding is the difficulty to find novel genes in genetically-inaccessible system like human brain. Another problem is the complexity of brain making it difficult to link cellular phenomena to behavior, which is necessary to understand brain. To solve these problems, a genetically-accessible model organism C. elegans was introduced. With only 302 neurons, nervous system of C. elegans still has many properties common to the higher animal’s brain, including usage of monoamines and their roles in neural plasticity. Studies so far in C. elegans have provided much information by using mutants, exogenous amine application and neuron ablation. However, these methods have not considered dynamic property of aminergic system. Here, the applicant uses the genetically-encoded light-gated cation channel channelrhodopsin-2 (ChR2). Because the body of C. elegans is transparent, by expressing and light-activating ChR2 specifically in aminergic neurons, one can examine the amine effectss on behavior with precise time resolution. The automated behavior quantification system makes it possible to identify any subtle behavioral changes caused by aminergic activation. The applicant will also examine the amine effects in cellular level, by live-imaging of downstream neuron activity with sensor protein cameleon. After identifying the amine effects, the applicant will start to dissect aminergic system with powerful genetics of C. elegans, which will provide a good starting point for further studies in future. This project for the first time allows us to examine the dynamic aspects of genetically-dissectable aminergic system, so it will contribute much to understanding aminergic system and also to European excellence in this promising and competitive field of C. elegans neurobiology.
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