| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1999: ¥3,100,000 (Direct Cost: ¥3,100,000)
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| Research Abstract |
The Ras-MAPK (mitogen-activated protein kinase) signal transduction pathway is well known to play a major role in the regulation of cellular proliferation and differentiation. In the model organism Caenorhabditis elegans, the Ras-MAPK pathway plays key roles in vulval induction, progression of meiosis, and several other developmental events1. However, although LET-60 Ras is expressed in many neurons2, its function in the nervous system is not known in this organism. Here we report that the Ras-MAPK pathway plays an essential role in olfactory neurons in C.elegans. Mutational inactivation and hyperactivation of this nathway impairs the chemotactic response of the animals to a set of odorants. The expression of wild type and a mutant form of let-60 ras by a heat shock promoter and a cell-specific promoter indicates that the normal activity of LET-60 is required in mature olfactory neurons. Application of the odorant isoamylalcohol to wild type animals leads to the activation of MAP kinas
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e in olfactory neurons within 10 seconds. This induction is dependent on the function of the nucleotide-gated channel TAX-2/TAX-4 and the voltage-activated calcium channel subunit UNC-2. These results suggest a dynamic role for the pathway in perception and transmission of sensory signals in olfactory neurons.
While the basic functions of the nervous system of Caenorhabditis elegans have been extensively studied, its behavioral plasticities are not fully explored due to the limited availability of assay systems. We report here a simple form of chemotaxis plasticity in this organism. When worms are starved on plates including NaCl, their chemotaxis to NaCl drops dramatically. This conditioning requires both the presence of NaCl and the absence of bacteria, indicating that it is not a mere adaptation or habituation, but is likely to be a form of associative learning. While chemotaxis to volatile chemoattractants does not change significantly after conditioning with NaCl, chemotaxis to other water-soluble attractants also decreased. This suggests that an altered response of a cell (s) specifically involved in chemotaxis to water-soluble chemoattractants is responsible for the behavioral alteration. The decrease in chemotaxis occurred slowly over 3-4 hours of conditioning and returned quickly to the original level when either of the conditioning stimuli, NaCl or starvation, was removed. The application of serotonin partially blocked this drop in chemotaxis, consistent with the proposed function of this neurotransmitter in food signaling. We have isolated three mutants with reduced plasticity as assayed in this paradigm. This assay system expands the opportunities in which molecular and cellular mechanisms of behavioral plasticity can be studied in C.elegans. Less
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