Elucidation of The Molecular Mechanims of Chemotaxis and Its Plasticity in the Nematode Caenorhabditis elegans

众所周知，Ras-MAPK(丝裂原活化蛋白激酶)信号转导通路在调节细胞增殖和分化中起着重要作用。在模式生物秀丽线虫中，Ras-MAPK通路在外阴诱导、减数分裂的进展和其他几个发育事件中起着关键作用。然而，尽管let-60RAS在许多神经元中表达，但它在神经系统中的功能在这种生物体中尚不清楚。在此，我们报道了Ras-MAPK通路在线虫嗅觉神经元中起着重要的作用。Nathway的突变失活和过度激活会损害动物对一系列气味的趋化反应。由热休克启动子和细胞特异性启动子表达的野生型和突变型let-60 ras表明，成熟的嗅神经元需要let-60的正常活性。异戊醇气味对野生型动物MAP激动素…的激活在10秒内嗅觉神经元有更多的电活动。这种诱导依赖于核苷酸门控通道TAX-2/TAX-4和电压激活的钙通道亚单位UNC-2的功能。这些结果表明，该通路在嗅神经元感知和传递感觉信号中起着动态作用。虽然秀丽线虫神经系统的基本功能已经得到了广泛的研究，但由于检测系统的有限，其行为可塑性还没有得到充分的研究。我们在这里报告了一种简单形式的趋化可塑性在这种有机体。当蠕虫在包括氯化钠在内的培养皿中挨饿时，它们对氯化钠的趋化性会急剧下降。这种条件作用既需要氯化钠的存在，也需要细菌的存在，这表明这不仅仅是一种适应或习惯化，而很可能是一种联想学习的形式。对挥发性化学引诱剂的趋化性经氯化钠处理后没有明显变化，但对其他水溶性引诱剂的趋化性也有所下降。这表明，参与趋化作用的细胞(S)对水溶性趋化物质的反应改变是导致行为改变的原因。趋化性的下降在3-4小时内缓慢发生，当去除任何一种条件刺激时，趋化能力迅速恢复到原来的水平。5-羟色胺的应用部分阻断了趋化性的下降，这与这种神经递质在食物信号中的功能是一致的。我们已经分离出三个可塑性降低的突变体，就像在这个范例中所分析的那样。这一检测系统扩大了研究线虫行为可塑性的分子和细胞机制的机会。较少

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 … More 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