We are using genetics and molecular biology in the nematode C. elegans to address the problem of attention: how does an organism filter out persistent stimuli while remaining responsive to a novel stimulus in its environment? Most neurons in the nervous system encounter this problem; they express receptors for several different neurotransmitters and, therefore, have the potential to respond to multiple transmitters. It is critical that signals from each receptor are integrated and regulated appropriately. C. elegans olfaction is an attractive system for studying neuronal signaling specificity and receptor down-regulation or adaptation as each sensory neuron is able to respond to a number of odorants and each odorant response is independently adapted. The goal of our work is to use the powerful genetics provided by C. elegans to uncover the circuits and molecular pathways responsible for regulating receptor signaling. Little is known about how lack of adaptation effects long-term neuronal changes. Changes that occur within the C. elegans olfactory circuit in response to unregulated signaling may parallel changes that occur during addiction in higher animals. Genetic, biochemical and genomic techniques will be utilized to identify the molecular changes that occur within neurons and circuits of neurons that fail to adapt and how these changes may be effected. Understanding neuronal plasticity in C. elegans will shed light on processes that allow mammalian neurons to respond appropriately to their environment.

Publications:

Kaye J.A., Rose N.C. Goldsworthy B., Goga A., L'Etoile N.D. (2009). A 3'UTR pumilio-binding element directs translational activation in olfactory sensory neurons. Neuron, 61:57-70.

L'Etoile, N.D., Coburn, C.M., Eastham, J.R., Kistler, A., Gallegos, G., and Bargmann, C.I. (2002). The cyclic GMP-dependent protein kinase EGL-4 regulates olfactory adaptation in C. elegans. Neuron, 36: 1079-1089.

Dwyer, N.D., Adler, C.E., Crump, J.G., L'Etoile, N.D., Bargmann, C.I. (2001). The AP-1 B1 clathrin adaptor UNC-101 mediates odorant receptor localization to olfactory cilia. Neuron, 31: 277-287.

L'Etoile, N.D., and Bargmann, C.I. (2000). Olfaction and Odor Discrimination are Mediated by the C elegans Guanylyl Cyclase ODR- 1. Neuron 25, 575-586.

Komatsu, H., Jin, Y.H., L'Etoile, N.D., Mori, I., Bargmann, C.I., Akaike, N., Ohshima, Y. (1999). Functional reconstitution of a heteromeric cyclic nucleotide-gated channel of Caenorhabditis elegans in cultured cells. Brain Res. 821, 160-168.

Martinez, E., Zhou, Q., L'Etoile, N.D., Oelgeschlager, T., Berk, A.J.,and Robert Roeder (1995). Core promoter-specific function of a mutant transcription factor TFIID defective in TATA-box binding. Proceedings of the National Academy of Sciences

L'Etoile, N.D., Fahnestock, M.L., Shen, Y., Aebersold, R., and Arnold J. Berk (1994). Human TFIIIC Box B-Binding Subunit. Proceedings of the National Academy of Sciences, 91, 1652-1656.

Boulanger, P.A., L'Etoile, N.D., and Arnold J. Berk (1989). A binding domain of human transcription factor IIIC2. Nucleic Acids Research 17, 7761-7770.

Yoshinaga, S.K., L'Etoile, N.D., and Arnold J. Berk (1989). Purification and characterization of transcription factor IIIC2. Journal of Biological Chemistry 264, 10726-10731.