Integrative analysis of serotonin-mediated behavioural phase transition in the desert locust

动物的行为、体型和颜色可能会因环境条件的不同而发生深刻的变化。这在生物学上提出了一个重大问题：动物生活的环境如何影响其基因的表达，并塑造其大脑功能、荷尔蒙，从而塑造其行为，从而使其适当地适应不断变化的环境。沙漠蝗虫展示了这种可塑性的极端例子；它可以可逆地从一种在夜间飞行的害羞、低调、孤独的生物变成一种非常显眼的白天飞行的生物，有时还会大量聚集，这会产生毁灭性的经济影响。这两种形式--独居阶段和群居阶段--在外表、生理和行为上都截然不同。它们可以在实验室中繁殖，并通过单独饲养或在群体中饲养，使它们从一个阶段切换到另一个阶段，然后再回来。他们大脑中的神经细胞相对较少，因此有可能理解在这些相变过程中发生的变化，并解释在更复杂的动物发现自己处于新环境时发生的类似机制。一只蝗虫必须做出的关键决定是加入或避开其他蝗虫。一旦这样做了，随后的生理、体型和颜色的变化就会随着其他蝗虫的持续存在或不存在而发生。通过挠挠独居蝗虫的后腿来模仿与其他蝗虫相互推搡的效果，或者模仿其他蝗虫的视觉和气味，可能会在1-2小时内导致这种行为变得合群。这种转变伴随着神经系统中许多化学物质的数量发生了实质性的变化。特别是，5-羟色胺(一种在人脑中会影响攻击性和抑郁等多种情绪的物质，其释放会受到摇头丸等药物的影响)显示出大量但短暂的增加，关键是，它既是必要的，也是充分的，可以诱导行为的改变。我们已经确定了哪些神经细胞的5-羟色胺水平发生了变化。我们现在希望了解5-羟色胺如何改变神经细胞的工作方式，从而带来行为的改变。为了实现这一目标，我们有以下关键目标：1.识别和描述在最初的行为改变期间改变其5-羟色胺产生的神经细胞。它们在中枢神经系统中延伸了多远？在其他蝗虫的存在下，它们是如何反应的？它们对其他神经细胞有什么影响，使行为发生变化？2.确定受5-羟色胺释放影响的神经细胞。5-羟色胺在这些神经细胞的内部工作中会引起什么化学变化？这将在特定分子的水平上进行检查，这些分子参与级联化学反应，在一个细胞内传递信息并传递给邻近细胞。3.5-羟色胺可以改变神经细胞之间交流的有效性和时间进程，为学习提供必要的基础。在拥挤经历之前、期间和之后，神经系统中不同数量的5-羟色胺如何影响神经细胞之间的交流？5-羟色胺对独居蝗虫和群居蝗虫有不同的影响吗？4.详细研究独居蝗虫和群居蝗虫在进食、探索环境和睡眠等日常活动模式上的不同，并开始研究调节它们生物钟的基因在这两个阶段的不同。5.群居的蝗虫如果被从人群中移走，很快就会恢复到独居的行为。维持他们群居行为的机制是什么？导致独居行为的互补过程是什么？

Animals may undergo profound changes in their behaviour, body shape and colour in response to varying environmental conditions. This poses a major problem in biology: how do the surroundings in which an animal lives, influence the expression of its genes and mould its brain function, its hormones, and hence its behaviour, so that it is appropriately adapted to changing circumstances. The Desert Locust shows an extreme example of this malleability; it can change reversibly from a shy and inconspicuous, solitary creature that flies at night to one that is highly conspicuous, day flying and occasionally aggregates in vast numbers which has devastating economic effects. These two forms - the solitarious and gregarious phases - are strikingly different in appearance, physiology and behaviour. They can be bred in the laboratory and made to switch from one phase to the other and back, by simply raising them in isolation or in a crowd. They have relatively few nerve cells in their brain so that it is possible to understand the changes that occur during these phase transitions and to illuminate the similar mechanisms that occur in more complex animals when they find themselves in new circumstances. The key decision a locust must make is to join with or avoid other locusts. Once this has been made subsequent changes in physiology, body shape and colour follow from the continuing presence or absence of other locusts. Tickling the hind legs of a solitarious locust to mimic the effects of jostling with others, or the sight and smell of other locusts, can, in 1-2 h, cause the behaviour to become gregarious. This transition is accompanied by substantial changes in the amounts of many chemicals in its nervous system. In particular serotonin (a substance that in human brains affects many moods such as aggression and depression, and the release of which is affected by drugs such as ecstasy) shows a large but short-lived increase and, critically, it is both necessary and sufficient to induce the change in behaviour. We have determined which nerve cells show changes in their serotonin levels. We now wish to understand how serotonin changes the workings of nerve cells to bring about the transformation of behaviour. To achieve this aim we have these key objectives: 1. Identify and characterise the nerve cells that change their production of serotonin during the initial change in behaviour. How far do they extend through the central nervous system? How do they respond in the presence of other locusts, and what effects do they have on other nerve cells to bring about changes in behaviour? 2. Identify the nerve cells that are influenced by the release of serotonin. What chemical changes does serotonin cause in the internal workings of these nerve cells? This will be examined at the level of specific molecules that engage in cascades of chemical reactions to pass information within one cell and to neighbours. 3. Serotonin can change the effectiveness and the time course of communication between nerve cells, providing an essential building block of learning. How do differing amounts of serotonin in the nervous system before, during and after the experience of crowding, affect communication between nerve cells? Does serotonin have different effects in solitarious and gregarious locusts? 4. Examine in detail how solitarious and gregarious locusts differ in their patterns of daily activity such as feeding, exploring their environment and sleeping, and begin to look at how genes that regulate their body clock differ in the two phases. 5. Gregarious locusts quickly revert to solitarious behaviour if they are removed from the crowd. What are the mechanisms that maintain their gregarious behaviour and what is the complimentary process that leads to solitarious behaviour?