Three distinct amine receptors operating at different levels within the locomotory circuit are each essential for the serotonergic modulation of chemosensation in Caenorhabditis elegans.
Three distinct amine receptors operating at different levels within the locomotory circuit are each essential for the serotonergic modulation of chemosensation in Caenorhabditis elegans.
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DOI：
10.1523/jneurosci.4585-08.2009
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发表时间：
2009-02-04
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影响因子：
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通讯作者：
Komuniecki RW
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文献类型：
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作者：
Harris GP;Hapiak VM;Wragg RT;Miller SB;Hughes LJ;Hobson RJ;Steven R;Bamber B;Komuniecki RW
5-羟色胺调节脊椎动物和无脊椎动物的行为可塑性，线虫通过至少四种不同的5-羟色胺受体调节关键行为，包括运动、厌恶学习和嗅觉。在本研究中，我们研究了含有这些5-羟色胺受体零等位基因的动物对稀辛醇的厌恶反应的5-羟色胺能刺激。与野生型、Ser-4或Ser-7缺失动物相比，Ser-1和mod-1缺失动物均不能增加食物/5-羟色胺对稀辛醇的敏感性。MOD-1和SER-1在MOD-1和Ser-1缺失动物的AIB或潜在的AIY和RIA中间神经元中的表达分别恢复了5-羟色胺的敏感性。由于这些5-羟色胺受体似乎都不表达在ASH感觉神经元中，介导辛醇敏感性，我们发现了一个5-HT6样受体F16D3.7(SER-5)，它是依赖食物/5-羟色胺增加辛醇敏感性所必需的。在食物/5-羟色胺存在的情况下，Ser-5缺失动物不能增加辛醇的敏感性，在ASHS中表达SER-5可以恢复其敏感性。同样，野生型动物ASHS中Ser-5表达的RNAi下调也消除了5-羟色胺依赖的辛醇敏感性增加，表明SER-5直接调节ASHS的辛醇反应。综上所述，这些结果表明，在运动回路中不同水平发挥作用的多个胺受体，每个都是ASH介导的厌恶反应的5-羟色胺能调制所必需的。
Serotonin modulates behavioral plasticity in both vertebrates and invertebrates and in Caenorhabditis elegans regulates key behaviors, including locomotion, aversive learning and olfaction through at least four different 5-HT receptors. In the present study, we examined the serotonergic stimulation of aversive responses to dilute octanol in animals containing null alleles of these 5-HT receptors. Both ser-1 and mod-1 null animals failed to increase sensitivity to dilute octanol on food/5-HT, in contrast to wild-type, ser-4 or ser-7 null animals. 5-HT sensitivity was restored by the expression of MOD-1 and SER-1 in the AIB or potentially the AIY, and RIA interneurons of mod-1 and ser-1 null animals, respectively. Since none of these 5-HT receptors appear to be expressed in the ASH sensory neurons mediating octanol sensitivity, we identified a 5-HT6-like receptor, F16D3.7(SER-5), that was required for food/5-HT dependent increases in octanol sensitivity. ser-5 null animals failed to increase octanol sensitivity in the presence of food/5-HT and sensitivity could be restored by expression of SER-5 in the ASHs. Similarly, the RNAi knockdown of ser-5 expression in the ASHs of wild-type animals also abolished 5-HT dependent increases in octanol sensitivity, suggesting that SER-5 modulates the octanol responsiveness of the ASHs directly. Together, these results suggest that multiple amine receptors, functioning at different levels within the locomotory circuit, are each essential for the serotonergic modulation of ASH-mediated aversive responses.