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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM083241-03
Application #
7786981
Study Section
Special Emphasis Panel (ZRG1-MDCN-K (90))
Program Officer
Tompkins, Laurie
Project Start
2008-05-05
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
3
Fiscal Year
2010
Total Cost
$305,910
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Physiology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Zhang, Bi; Gong, Jianke; Zhang, Wenyuan et al. (2018) Brain-gut communications via distinct neuroendocrine signals bidirectionally regulate longevity in C. elegans. Genes Dev 32:258-270
Jun, Heejin; Yu, Hui; Gong, Jianke et al. (2018) An immune-beige adipocyte communication via nicotinic acetylcholine receptor signaling. Nat Med 24:814-822
Rauthan, Manish; Gong, Jianke; Liu, Jinzhi et al. (2017) MicroRNA Regulation of nAChR Expression and Nicotine-Dependent Behavior in C. elegans. Cell Rep 21:1434-1441
Li, Zhaoyu; Iliff, Adam J; Xu, X Z Shawn (2016) An Elegant Circuit for Balancing Risk and Reward. Neuron 92:933-935
Chaudhuri, Jyotiska; Bose, Neelanjan; Gong, Jianke et al. (2016) A Caenorhabditis elegans Model Elucidates a Conserved Role for TRPA1-Nrf Signaling in Reactive ?-Dicarbonyl Detoxification. Curr Biol 26:3014-3025
Li, Guang; Gong, Jianke; Lei, Haoyun et al. (2016) Promotion of behavior and neuronal function by reactive oxygen species in C. elegans. Nat Commun 7:13234
Wang, Xiang; Li, Guang; Liu, Jie et al. (2016) TMC-1 Mediates Alkaline Sensation in C. elegans through Nociceptive Neurons. Neuron 91:146-54
Wescott, Seth A; Ronan, Elizabeth A; Xu, X Z Shawn (2016) Insulin signaling genes modulate nicotine-induced behavioral responses in Caenorhabditis elegans. Behav Pharmacol 27:44-9
Gong, Jianke; Yuan, Yiyuan; Ward, Alex et al. (2016) The C. elegans Taste Receptor Homolog LITE-1 Is a Photoreceptor. Cell 167:1252-1263.e10
Chun, Lei; Gong, Jianke; Yuan, Fengling et al. (2015) Metabotropic GABA signalling modulates longevity in C. elegans. Nat Commun 6:8828

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