To respond appropriately to its dynamic environment, a sensory neuron must attenuate its response to persistent stimuli while remaining sensitive to a novel stimulus. This is accomplished by specifically turning down or adapting, the response of the receptor. Accurate adaptation of signaling events is crucial throughout the nervous system; failure to down-regulate the G-protein coupled receptor (GPCR) rhodopsin signaling leads to retinal degeneration and blindness in Oguchi disease (Chen et al., 1999) while hyperadaptation of the mu opioid GPCR signaling by morphine leads to tolerance associated with opiate addiction (Whistler et al., 1998). Though the initial signal transduction events and rapid turn off of such GPCR-mediated signaling are well described, little is known about how these neurons adapt to prolonged stimulation. In this grant, we propose to identify the molecules and molecular processes responsible for long lasting adaptation of GPCR signaling in C. elegans. Study of a model organism that is tractable to both genetics and cell biology affords us the opportunity to examine the molecular processes that deactivate odor signaling. We will use cell biological techniques to examine the initiation of long-term adaptation by the PKG, EGL-4. In so doing, we will characterize the role that such basic biological processes as transcription, and endocytosis play in promoting adaptation. Finally, we will identify new molecules required to initiate adaptation of a GPCR signaling. Biophysical, biochemical, and protein trafficking changes that regulate adaptation in C. elegans sensory neurons are likely to have their counterparts in the mammalian central nervous system. The genes identified as being important for initiating long-term adaptation are likely to have conserved functions in diverse cell types that rely on adaptation-like processes to respond to prolonged or repeated signaling.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
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Synapses, Cytoskeleton and Trafficking Study Section (SYN)
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Davis, Barry
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University of California Davis
Schools of Arts and Sciences
United States
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O'Halloran, Damien M; Altshuler-Keylin, Svetlana; Zhang, Xiao-Dong et al. (2017) Contribution of the cyclic nucleotide gated channel subunit, CNG-3, to olfactory plasticity in Caenorhabditis elegans. Sci Rep 7:169
Cho, Christine E; Brueggemann, Chantal; L'Etoile, Noelle D et al. (2016) Parallel encoding of sensory history and behavioral preference during Caenorhabditis elegans olfactory learning. Elife 5:
He, Chao; Altshuler-Keylin, Svetlana; Daniel, David et al. (2016) The cyclic nucleotide gated channel subunit CNG-1 instructs behavioral outputs in Caenorhabditis elegans by coincidence detection of nutritional status and olfactory input. Neurosci Lett 632:71-8
Juang, Bi-Tzen; Ludwig, Anna L; Benedetti, Kelli L et al. (2014) Expression of an expanded CGG-repeat RNA in a single pair of primary sensory neurons impairs olfactory adaptation in Caenorhabditis elegans. Hum Mol Genet 23:4945-59
Juang, Bi-Tzen; Gu, Chen; Starnes, Linda et al. (2013) Endogenous nuclear RNAi mediates behavioral adaptation to odor. Cell 154:1010-1022
Krzyzanowski, Michelle C; Brueggemann, Chantal; Ezak, Meredith J et al. (2013) The C. elegans cGMP-dependent protein kinase EGL-4 regulates nociceptive behavioral sensitivity. PLoS Genet 9:e1003619
O'Halloran, Damien M; Hamilton, O Scott; Lee, Jin I et al. (2012) Changes in cGMP levels affect the localization of EGL-4 in AWC in Caenorhabditis elegans. PLoS One 7:e31614
Swarbrick, Alexander; Woods, Susan L; Shaw, Alexander et al. (2010) miR-380-5p represses p53 to control cellular survival and is associated with poor outcome in MYCN-amplified neuroblastoma. Nat Med 16:1134-40
Kaye, Julia A; Rose, Natalie C; Goldsworthy, Brett et al. (2009) A 3'UTR pumilio-binding element directs translational activation in olfactory sensory neurons. Neuron 61:57-70
O'Halloran, Damien M; Altshuler-Keylin, Svetlana; Lee, Jin I et al. (2009) Regulators of AWC-mediated olfactory plasticity in Caenorhabditis elegans. PLoS Genet 5:e1000761