Cornelia I. Bargmann
Development and function of the olfactory system
An animal's ability to recognize and discriminate among different sensory stimuli allows it to generate diverse behavioral responses to its environment. We are studying olfactory recognition and olfactory development in the nematode C. elegans using genetic, cellular and molecular approaches.
To ask about the biochemistry of odorant recognition, we used genetic approaches to define a specific olfactory receptor-ligand interaction. A genetic screen for animals with defective responses to the odorant diacetyl yielded the odr-10 gene, which encodes a predicted G protein-coupled receptor. Based on its genetic and molecular properties, ODR-10 is likely to be a specific receptor for diacetyl. We also found that C. elegans may have as many as 1000 olfactory receptor genes in five different gene families, explaining its ability to recognize many odorants.
C. elegans olfactory neurons use two different signal transduction pathways to convert receptor binding into electrical activity, one that involves a cGMP-gated channel and one that involves a TRP-related channel. We are studying these pathways and their regulation to understand how sensory information is integrated and how behaviors are changed by experience.
The odorant diacetyl is always attractive to wild-type animals. This behavioral specificity could reflect a property of odr-10, the diacetyl receptor, or a property of the AWA olfactory neurons that express odr-10. To distinguish between these models, we expressed odr-10 in the AWB olfactory neurons, which detect repellents. When odr-10 is expressed in AWB, the resulting transgenic animals avoid diacetyl. These results indicate that the receptor is not intrinsically coupled to attractive behaviors. Rather, the AWA neurons recognize attractants and the AWB neurons recognize repellents: each neuron interprets the odorants that it detects in a stereotypic fashion.
Natural variation in sensory behaviors is observed in many animals. We have discovered a polymorphism in wild C. elegans populations that leads to distinct solitary or social behavior patterns. The gene responsible for this behavioral variation encodes a neuropeptide receptor that interacts with the olfactory signalling pathways. We are also studying axon guidance and synapse formation by the olfactory neurons. A novel conserved receptor in the immunoglobulin gene family is essential in olfactory axon guidance; this protein, SAX-3/Robo, is highly similar to fly and mammalian Robo genes that seem to have similar functions. Neuronal activity also affects axon outgrowth in the C. elegans olfactory system, and appears to refine or maintain connections made during initial guidance.