High-throughput Mapping of Brain-wide Activities in Live and Drug-responsive Vertebrates
DescriptionDespite the tremendous demands for effective drugs to treat many devastating braindiseases, only 7% of neurological drugs in clinical development reach the marketplace in theend. The causes for such low success rate mainly lie in facts: first, the presence of a uniqueand dramatic complexity in human brain; second, the lack of key technologies that canrapidly assess large scale library of drug leads in brains of awake animals. Ideally, theevaluation of lead chemicals needs to correlate the activation of specific neurons with theexecution of specific behaviors under normal or drug treated conditions, which is commonlyreferred as brain activity map. The capability to perform high-throughput monitoring of brainactivities with sufficient temporal and spatial resolution in live vertebrate animals would beinvaluable for both basic and translational neuroscience research. Toward this goal, animmediate and achievable step is to work with an animal model, such as zebrafish, that hassmaller and simpler neurocircuitry, and is amenable to large-scale high-throughput screening.Using genetically modified zebrafish as a working model, this proposed project aims toaddress several key challenges by combining different electrical and biomedical engineeringapproaches, including microfluidics, robotic automation, image & signal processing, calciumimaging & analysis, and transgenic modification, to develop an innovative system that iscapable of high-throughput mapping of brain-wide activities in awake zebrafish in responseto acute drug stimuli. It’s expected that success of this project will provide a novel tool forstudy brain functions involving real-time interactions of large sets of neurons, and also createa new paradigm for drug screening and discovery for neurological diseases and disorders.
|Effective start/end date||1/01/15 → 28/12/18|
- brain activity map,high-throughput screening,calcium imaging,lab on a chip,