Regulation of extrasynaptic 5-HT by serotonin reuptake transporter function in 5-HT-absorbing neurons underscores adaptation behavior in Caenorhabditis elegans.
Regulation of extrasynaptic 5-HT by serotonin reuptake transporter function in 5-HT-absorbing neurons underscores adaptation behavior in Caenorhabditis elegans.
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DOI：
10.1523/jneurosci.1692-11.2011
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发表时间：
2011-06-15
期刊：
影响因子：
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通讯作者：
Sze JY
中科院分区：
文献类型：
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作者：
Jafari G;Xie Y;Kullyev A;Liang B;Sze JY
5-羟色胺（5-HT）吸收神经元通过5-羟色胺再摄取转运蛋白（SERT）从细胞外空间摄取5-HT，但不合成5-HT。对于人类来说，它们的功能尚未阐明。在这里，我们表明，在5-HT吸收神经元的SERT控制的行为反应，食物剥夺C。优雅的。AIM和RIH中间神经元摄取化学感受神经元和分泌神经元释放的5-HT。遗传分析表明，5-HT分泌的突触囊泡和致密的核心囊泡容易扩散到突触外空间相邻的AIM和RIH神经元。mod-5/SERT功能的丧失阻断了5-HT的吸收。mod-5/SERT突变体显示出对食物剥夺的过度运动反应。我们发现MOD-5/SERT在5-HT吸收神经元中的转基因表达完全纠正了夸张的行为。细胞特异性抑制突触传递的实验表明，从5-HT吸收神经元的5-HT的突触释放是不需要这种行为调制。我们的数据点的作用，5-HT吸收神经元作为突触外5-HT的时空调节器。5-HT吸收神经元对突触外5-HT水平的调节可能是5-HT稳态的一个基本机制，它将5-HT产生神经元的活性与神经回路中的远距离靶点整合在一起，并可能与SSRIs在人体中的某些作用有关。
Serotonin (5-HT)-absorbing neurons use serotonin reuptake transporter (SERT) to uptake serotonin (5-HT) from extracellular space but do not synthesize it. While 5-HT-absorbing neurons have been identified in diverse organisms from C. elegans to humans, their function has not been elucidated. Here, we show that SERT in 5-HT-absorbing neurons controls behavioral response to food deprivation in C. elegans. The AIM and RIH interneurons uptake 5-HT released from chemosensory neurons and secretory neurons. Genetic analyses suggest that 5-HT secreted by both synaptic vesicles and dense core vesicles diffuse readily to the extrasynaptic space adjacent to the AIM and RIH neurons. Loss of mod-5/SERT function blocks the 5-HT absorption. mod-5/SERT mutants have been shown to exhibit exaggerated locomotor response to food deprivation. We found that transgenic expression of MOD-5/SERT in the 5-HT-absorbing neurons fully corrected the exaggerated behavior. Experiments of cell-specific inhibition of synaptic transmission suggest that the synaptic release of 5-HT from the 5-HT-absorbing neurons is not required for this behavioral modulation. Our data point to the role of 5-HT-absorbing neurons as temporal-spatial regulators of extrasynaptic 5-HT. Regulation of extrasynaptic 5-HT levels by 5-HT-absorbing neurons may represent a fundamental mechanism of 5-HT homeostasis, integrating the activity of 5-HT-producing neurons with distant targets in the neural circuits, and could be relevant to some actions of SSRIs in human.