Neural circuits are the functional and structural units of the nervous system. Defects in neural circuit function and development lead to a variety of neurological disorders. We are interested in understanding how information is processed by neural circuits and how genes regulate such processing, and how this ultimately produces and reshapes behavioral output. As numerous neural mechanisms are found to be conserved across phylogeny, genetic model organisms, such as C. elegans and Drosophila, have been widely utilized to study various phenomena in neurobiology. About two-third of human disease genes have homologs in these organisms. However, certain technological shortfalls have greatly hampered the use of these genetic organisms as a model for neurobiology research. In particular, there is no technology available that allows one to record neural activity in behaving worms or flies. Consequently, all current studies have been limited to recording neural activity in immobilized or semi-immobilized, but not in freely-behaving animals, making it difficult to reliably correlate neural activity and behavior. Here we have, for the first time, developed a novel noninvasive neuroimaging system that can record neuronal activity in freely-behaving worms at single neuron resolution, thus allowing for mapping the neural circuits underlying behavior. In the current proposal, by taking advantage of this novel neuroimaging system in conjunction with laser microsurgery and molecular genetic tools, we will define the neural circuits underlying some classic worm behaviors. In addition, we will further develop the system by introducing more advanced functionalities. The proposed work will provide novel insights into how the nervous system and genes control behavior in mammals. Many types of neurological disorders (e.g., epilepsy, movement disorders and bipolar disorder) are manifested by behavioral abnormalities that result from defective neural circuit function and development. Our work will provide novel insights into how neural circuits and genes control normal behavior and how defects in this process lead to those neurological disorders.
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