Student Theses and Dissertations

Heeun Jang

Date of Award

2012

Document Type

Thesis

RU Laboratory

Bargmann Laboratory

Abstract

Social behavior is a widespread phenomenon across species from microorganisms to humans. Chemical communication using pheromones is particularly interesting for its versatile use in many organisms, and has been studied at both molecular and circuit levels. However, the central issue of how genes and molecular components contribute to neural circuits that eventually lead to complex social behaviors remains unclear. Using the nematode model organism Caenorhabditis elegans, I have examined two behavioral responses to pheromones, pheromone avoidance and pheromoneregulated social aggregation behavior, at genetic and circuit levels. The known C. elegans pheromones are a set of related compounds called ascarosides. Specific ascarosides are known to regulate development and male attraction to potential mates. To characterize hermaphrodite responses to ascarosides, I used a behavioral assay for acute avoidance called the drop test, which measures reversals of a forward-moving worm upon an encounter with a diluted pheromone. I found that wildtype hermaphrodites from the laboratory N2 strain avoid one of the ascarosides, ascr#3/C9. Through in vivo functional imaging using a genetically encoded calcium sensor and behavioral analysis of sensory mutants, I found that the nociceptive ADL neurons sense ascr#3/C9. Behavioral analysis of synaptically manipulated worms indicated that ADL chemical synapses promotes avoidance behavior. Animals with null mutation in the neuropeptide receptor npr-1 have reduced avoidance of ascr#3/C9. I found that this effect is mediated by ADL participation in a gap junction circuit with the “social” hub interneuron RMG. Thus ADL chemical synapses and ADL gap junctions appear to have antagonistic effects on behavior. Avoidance is further suppressed by another modulatory ascaroside cue, ascr#5/C3, sensed by the ASK sensory neurons that are also connected to RMG by gap junctions. Males do not avoid ascr#3/C9, and they have reduced ADL sensory responses to this ascaroside. Genetic masculinization of ADL does not reduce its sensory responses, suggesting that the sensory change has a non-autonomous component. npr-1 males appear to be attracted to ascr#3/C9, and in these animals ASK strongly responds to ascr#3/C9 and contributes to the switch in behavioral responses. Together, these results indicate that behavioral avoidance of the pheromone ascr#3/C9 is modulated by neuropeptide signaling and sexual dimorphism that change neuronal properties at the circuit level. Invertebrate gap junctions are comprised of innexin subunits. I conducted a systematic genetic study to identify innexin genes that affect npr-1-dependent aggregation. Several weak suppressors of npr-1 aggregation behavior were identified, suggesting functional redundancy between innexins. In addition, I found that an allele of glb-5 present in the wild strain CB4856 suppresses aggregation, probably by modulating sensitivity to oxygen in oxygen-sensing neurons that promote aggregation. My thesis work should help expand our understanding of neural circuits and molecules used for chemical communication, simple animal social behaviors, and perhaps complex human behaviors.

Comments

A thesis presented to the faculty of The Rockefeller University in partial fulfillment of the requirements for the degree of Doctor of Philosophy.

Permanent URL

http://hdl.handle.net/10209/523

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