# Molecular and Behavioral Mechanisms of Aversive Olfactory Learning in C. elegans

 Title: Molecular and Behavioral Mechanisms of Aversive Olfactory Learning in C. elegans Author: Zhang, Xiaodong Citation: Zhang, Xiaodong. 2011. Molecular and Behavioral Mechanisms of Aversive Olfactory Learning in C. elegans. Doctoral dissertation, Harvard University. Access Status: Full text of the requested work is not available in DASH at this time (“dark deposit”). For more information on dark deposits, see our FAQ. Full Text & Related Files: Zhang_gsas.harvard_0084L_10030.pdf (8.632Mb; PDF) Abstract: The mechanisms of learning and memory are fundamental to our understanding of brain function. The aim of this thesis is to characterize the molecular, cellular and behavioral mechanisms underlying the aversive olfactory learning in the model organism C. elegans, to gain insight into animal learning in general. At the molecular level, I focused on the function of the transforming growth factor-$$\beta$$ $$(TGF-\beta)$$ signaling pathway. The $$TGF-\beta$$ pathway is conserved throughout the Metazoa and is critical for diverse physiological processes. It has also been implicated in neural plasticity, but the exact mechanisms remain elusive. Utilizing a behavioral assay that measures adult olfactory learning, I have found that DBL-1, a C. elegans $$TGF-\beta$$ homolog, is required for learned olfactory avoidance of pathogenic bacteria. Mutations in DBL-1 signal transduction pathway, including those in the dbl-1 ligand, sma-6 and daf-4 receptors, and sma-3 SMAD, abolish the learning ability of adult animals. I have identified AVA neurons, a pair of command interneurons critical for olfactory sensorimotor response, as the essential release site of DBL-1 ligand in regulating learning. AVA neuronal activity is repressed by training, accompanied by an increase in the amount of DBL-1 secreted from AVA neurons after training. Remarkably, artificial inhibition of AVA activity in the absence of training is sufficient to increase AVA secretion of DBL-1, supporting a model in which experience dependent changes in neuronal activity lead to altered DBL-1 $$TGF-\beta$$ signaling. Downstream of DBL-1 ligand, I found that the type I receptor SMA-6 primarily acts in the hypodermis to promote olfactory plasticity at the adult stage. At the behavioral level, I examined the taxis behavior of C. elegans toward different bacteria and the effect of training on its taxis strategy. Preliminary results suggest that C. elegans may be capable of modulating its olfactory preference by means of differentially adjusting its navigation strategy. In summary, this thesis uncovered the critical role of DBL-1 $$TGF-\beta$$ signaling in C. elegans learning, and alterations in behavioral components underlying olfactory plasticity. These findings are expected to shed light on learning and memory in other animals as well. Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10336888 Downloads of this work: