Regulation of neural circuits for oxygen-dependent behaviors in Caenorhabditis elegans.

摘要

Behavior, an organism's ability to sense and respond to its environment, is paramount to its survival in nature. In multicellular animals, behavior is generated by the nervous system. Innate genetic programs form neural circuits that are sensitive to the environment and experience.; To understand the function of the nervous system at a systems level, I have chosen the soil nematode Caenorhabditis elegans as a model animal. In this dissertation, I describe neural circuits underlying C. elegans behaviors towards an important sensory cue, oxygen, using a genetic and neuroanatomical approach.; In the absence of bacterial food, wild-type adult hermaphrodites of the N2 strain prefer 7-14% oxygen in a linear 0-21% oxygen gradient, avoiding higher and lower oxygen levels. In Chapter 2, I define a chemosensory circuit for hyperoxia avoidance (>14% oxygen) and its regulation by food. In N2 animals, hyperoxia avoidance is mediated by two groups of neurons that express soluble guanylate cyclase homologs and two groups of neurons that express TRPV channels. The presence of bacterial food suppresses hyperoxia avoidance of N2 animals. This modulation is regulated by NPR-1 neuropeptide signaling, the DAF-7 (TGF-beta) transcriptional pathway, and serotonin in distinct groups of neurons. The distributed nature of this chemosensory circuit resembles dynamic modulated networks from more complex nervous systems.; In Chapter 3, I describe effects of a transcriptional oxygen-sensing pathway on hyperoxia avoidance behavior of C. elegans. The hypoxia-inducible factor-1 (HIF-1) pathway is a conserved transcriptional pathway for oxygen homeostasis in metazoa. Upregulation of HIF-1 signaling alters the chemosensory circuit for hyperoxia avoidance in C. elegans and suppresses food regulation.; In Chapter 4, I show that hypoxia avoidance (avoidance of 4% oxygen) requires signaling through the TAX-4/TAX-2 cyclic nucleotide-gated channel in sensory neurons and normal regulation of the HIF-1 pathway, and appears genetically distinct from hyperoxia avoidance. These preliminary results suggest that C. elegans behaviors can be used to identify additional acute sensors of oxygen.