Neural circuits are assembled from a group of neurons via specific synaptic connections, and are the functional and structural units of the nervous system. Abnormal neural circuit and synaptic function lead to many types of neurological disorders. We are interested in mapping the functional components of neural circuits, dissecting the synaptic mechanisms by which the circuits process information, and understanding how genes regulate this process and how this ultimately produces and reshapes behavioral output. Given the immense complexity of the human nervous system and its inaccessibility to genetic manipulation, genetic model organisms with a relatively simple nervous system, such as C. elegans and Drosophila, have been widely used to investigate these questions. C. elegans has recently emerged as an increasingly popular genetic model for studying various phenomena in neurobiology, due to its simple and well characterized nervous system and amenability to genetic manipulation. Notably, C. elegans represents the only organism whose connectome (wiring diagram of its entire nervous system) is known. Additionally, many basic principles governing neural signaling, processing and development are conserved in C. elegans. About two-third of human disease genes have homologs in this organism. However, it remains largely enigmatic how the C. elegans nervous system is functionally organized to generate behaviors. We have recently developed an automated calcium imaging system that allows recording of neural activity in freely-behaving animals. We have also developed a multidisciplinary approach to map the neural circuits underlying behavior by integrating functional imaging, optogenetic interrogation, genetic manipulation, laser ablation, and electrophysiology. Using this approach, we will map the functional components of motor circuits, investigate the synaptic mechanisms by which the circuits process information, and characterize how sensory cues regulate the circuit dynamics to modulate behavioral output. As the microcircuits and the synaptic mechanisms employed by worms to process information show striking similarities to those by mammals, our study will provide novel insights into the neural basis of behavior in higher organisms.

Public Health Relevance

Many types of neurological disorders (e.g. epilepsy, movement disorders and bipolar disorder) are manifested by behavioral abnormalities that result from defective functions and development of neural circuits and synapses. Our work will provide novel insights into how neural circuits, synapses 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 #
5R01GM083241-06
Application #
8629763
Study Section
Synapses, Cytoskeleton and Trafficking Study Section (SYN)
Program Officer
Sesma, Michael A
Project Start
2008-05-05
Project End
2017-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
6
Fiscal Year
2014
Total Cost
$382,091
Indirect Cost
$132,093
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
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
Wang, Xiang; Li, Guang; Liu, Jie et al. (2016) TMC-1 Mediates Alkaline Sensation in C. elegans through Nociceptive Neurons. Neuron 91:146-54
Xiao, Rui; Chun, Lei; Ronan, Elizabeth A et al. (2015) RNAi Interrogation of Dietary Modulation of Development, Metabolism, Behavior, and Aging in C. elegans. Cell Rep 11:1123-33
Hardaway, J Andrew; Sturgeon, Sarah M; Snarrenberg, Chelsea L et al. (2015) Glial Expression of the Caenorhabditis elegans Gene swip-10 Supports Glutamate Dependent Control of Extrasynaptic Dopamine Signaling. J Neurosci 35:9409-23
Xiao, Rui; Liu, Jianfeng; Xu, X Z Shawn (2015) Thermosensation and longevity. J Comp Physiol A Neuroethol Sens Neural Behav Physiol 201:857-67
Chun, Lei; Gong, Jianke; Yuan, Fengling et al. (2015) Metabotropic GABA signalling modulates longevity in C. elegans. Nat Commun 6:8828
Yadlapalli, Swathi; Wani, Khursheed A; Xu, X Z Shawn (2014) Past experience resets behavior: CaMK takes the heat. Neuron 84:883-5
Li, Zhaoyu; Liu, Jie; Zheng, Maohua et al. (2014) Encoding of both analog- and digital-like behavioral outputs by one C. elegans interneuron. Cell 159:751-65
Wescott, Seth A; Rauthan, Manish; Xu, X Z Shawn (2013) When a TRP goes bad: transient receptor potential channels in addiction. Life Sci 92:410-4
Xiao, Rui; Zhang, Bi; Dong, Yongming et al. (2013) A genetic program promotes C. elegans longevity at cold temperatures via a thermosensitive TRP channel. Cell 152:806-17

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