The long-term objective of the proposed research is to understand how the nervous system controls behavior. This question has significant implications for mental health, for mental illness is, ultimately, a disease of behavior. Taking a model systems approach, we will study the neuronal basis of behavior in the nematode worm Caenorhabditis elegans. The existence of a complete description of the synaptic connectivity of the 302 neurons of the C. elegans nervous system, and the wide range of genetic and physiological techniques for linking genes and neurons to behavior in this animal, makes it unusually well-suited to the proposed studies. In addition, more than 60% of all human disease genes have a correlate in C. elegans, including genes implicated in devastating neurodegenerative conditions such as Parkinson's, Alzheimer's, and Lou Gehrig's disease. The present proposal focuses on chemotaxis -locomotion oriented to a chemical gradient -a simple example of the important problem of how sensory information is transformed by movement control centers to generate adaptive behavior. We have previously shown that chemotaxis in C. elegans follows a well-defined rule: turn more frequently when going down the gradient, and turn less frequently when going up the gradient. Other researchers have identified a network of neurons that controls the decision to go straight or to turn, but it is not yet known how this network functions in chemotaxis. We will address this question using a remarkable combination of genetics, electrophysiology, calcium imaging, and behavioral analysis to test a mathematical model of locomotory regulation. The proposed research is significant because locomotion defects are one of the main consequences of altering the function of neurodegenerative disease genes in C. elegans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH051383-17
Application #
7990449
Study Section
Sensorimotor Integration Study Section (SMI)
Program Officer
Glanzman, Dennis L
Project Start
1994-05-01
Project End
2012-02-29
Budget Start
2010-12-01
Budget End
2012-02-29
Support Year
17
Fiscal Year
2011
Total Cost
$329,670
Indirect Cost
Name
University of Oregon
Department
Neurosciences
Type
Schools of Arts and Sciences
DUNS #
948117312
City
Eugene
State
OR
Country
United States
Zip Code
97403
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Heckscher, Ellie S; Zarin, Aref Arzan; Faumont, Serge et al. (2015) Even-Skipped(+) Interneurons Are Core Components of a Sensorimotor Circuit that Maintains Left-Right Symmetric Muscle Contraction Amplitude. Neuron 88:314-29
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Faumont, Serge; Rondeau, Gary; Thiele, Tod R et al. (2011) An image-free opto-mechanical system for creating virtual environments and imaging neuronal activity in freely moving Caenorhabditis elegans. PLoS One 6:e24666
Lindsay, Theodore H; Thiele, Tod R; Lockery, Shawn R (2011) Optogenetic analysis of synaptic transmission in the central nervous system of the nematode Caenorhabditis elegans. Nat Commun 2:306
McCormick, Kathryn E; Gaertner, Bryn E; Sottile, Matthew et al. (2011) Microfluidic devices for analysis of spatial orientation behaviors in semi-restrained Caenorhabditis elegans. PLoS One 6:e25710
Lockery, Shawn R (2011) The computational worm: spatial orientation and its neuronal basis in C. elegans. Curr Opin Neurobiol 21:782-90
Singh, Komudi; Chao, Michael Y; Somers, Gerard A et al. (2011) C. elegans Notch signaling regulates adult chemosensory response and larval molting quiescence. Curr Biol 21:825-34

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