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High-resolution imaging of small animal models such as C. elegans, Drosophila larvae, and zebrafish larvae has become an indispensable tool in the study of long-term in vivo neural activities and functional imaging of the nervous systems. C. elegans with small body size and ability to grow in a liquid environment is suitable for optofluidic instrumentation and the whole-animal neuronal biophysics studies. Imaging platforms suitable for tracking behavior and cellular processes in C. elegans lack the ability to track sub-cellular processes that require high spatial and temporal resolutions. In neurons, essential processes such as axonal transport can be studied by acquiring fast time-lapse images of GFP-tagged cargoes. We have developed an imaging platform to track mitochondrial transport in unanesthetized intact animals that contribute to the long-term mitochondrial distribution in an individual developing neuronal process. In order to record the neuronal activities from the whole nervous system in the C. elegans, we developed a high-speed confocal imaging system. Using the 3D volumetric imaging system we studied functional connections and information flow through the connectome when the animal is exposed to external stimuli. In my last part of the talk, I will describe a large-scale imaging platform to enable both high-throughput and high-resolution imaging of multiple C. elegans populations. This platform can image 15 z-stacks of ~4,000 C. elegans from 96 different populations using a single chip with a micron resolution in 16 min. Using our platform, we screened ~1,000 FDA approved drugs in improving the aggregation phenotype of a polyglutamine aggregation model to identify possible proteostasis modulators, resulting in potential hits. |