Behavioral plasticity and the underlying neuronal plasticity represent a fundamental capacity of animals to cope with environmental stimuli. Behavioral plasticity is controlled by complex molecular networks that act under different layers of regulation. While various molecules have been found to be involved in the regulation of plastic behaviors across species, less is known about how organisms orchestrate the activity of these molecules as part of a coherent behavioral response to varying environments. Here we discover a mechanism for the regulation of animal behavioral plasticity involving molecular sulfation in brain, a modification of substrate molecules by sulfotransferase (ST)-catalyzed addition of a sulfonate group (SO3) from an obligate donor, 3’-phosphoadenosine 5’-phosphosulfate (PAPS) to the substrates. We investigated aggregation behaviors of the migratory locusts, which are well-known for extreme phase change plasticity triggered by population density. The processes of PAPS biosynthesis acted efficiently on induction of locust behavioral transition: Inhibition of PAPS synthesis solicited a behavioral shift from gregarious to solitarious states; external PAPS dosage, by contrast, promoted aggregation in solitarious locusts. Genetic or pharmacological intervention in the sulfation catalyzation resulted into pronounced solitarizing effects. Analysis of substrate-specific STs suggests a widespread involvement of sulfated neurotransmitters in the behavioral response. Dopamine in brain was finally identified to be actively sulfate conjugated, and the sulfate conjugation enhanced the free DA-mediated behavioral aggregation. Similar results in Caenorhabditis elegans and mouse indicate that sulfation may be involved more broadly in the modulation of animal aggregation. These findings revealed a general mechanism that effectively regulates animal social-like behavioral plasticity possibly through sulfation-mediated modification of neural networks.

中文翻译：

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大脑中多巴胺的硫酸化修饰调节动物的聚集行为

行为可塑性和潜在的神经元可塑性代表了动物应对环境刺激的基本能力。行为可塑性由复杂的分子网络控制，这些分子网络在不同的监管层下起作用。虽然已经发现各种分子参与调节跨物种的塑料行为，但对于生物体如何协调这些分子的活动作为对不同环境的连贯行为反应的一部分知之甚少。在这里，我们发现了一种调节动物行为可塑性的机制，涉及大脑中的分子硫酸化，通过磺基转移酶 (ST) 催化添加来自专性供体 3'-磷酸腺苷 5'- 的磺酸基 (SO3) 修饰底物分子磷酸硫酸盐 (PAPS) 到底物上。我们研究了迁徙蝗虫的聚集行为，这些行为以种群密度引发的极端相变可塑性而闻名。PAPS 生物合成过程有效地诱导了蝗虫的行为转变：抑制 PAPS 合成引起了从群居状态到独居状态的行为转变；相比之下，外部 PAPS 剂量促进了独居蝗虫的聚集。硫酸化催化中的遗传或药理学干预导致明显的孤立效应。对底物特异性 ST 的分析表明，硫酸化神经递质广泛参与行为反应。最终确定大脑中的多巴胺与硫酸盐结合，硫酸盐结合增强了游离 DA 介导的行为聚集。在秀丽隐杆线虫和小鼠中的类似结果表明硫酸化可能更广泛地参与动物聚集的调节。这些发现揭示了一种可能通过硫酸化介导的神经网络修饰来有效调节动物类社会行为可塑性的一般机制。