Behavioural Physiological and Molecular Mechanisms of Phase Change in Locusts

随着环境条件的变化，许多动物在形态和功能上都发生了深刻的变化，沙漠蝗虫就是一个臭名昭著的例子。它可以可逆地从一个神秘的孤独的生命形式变成一个成群的形式，偶尔聚集成大量的，造成毁灭性的影响。这两种形式是独居阶段和群居阶段，在外表、生理和行为上都有很大的不同。由于神经科学的一个主要目标是了解神经系统的改变是如何支撑行为变化的，因此蝗虫的相变是实现这一目标的一个强大的模型系统。我们在这项研究提案中的目的有三个。第一个是了解其他蝗虫提供的信号如何作用于孤独蝗虫的中枢神经系统，并开始修改神经细胞之间的连接，使以前孤独的蝗虫在第一次接触后4小时内表现得像群居蝗虫。我们已经知道，其他蝗虫提供的触摸信号会驱动行为区划，这些信号会触发中枢神经系统中两种物质的释放。我们希望知道触摸刺激如何导致这些物质--5-羟色胺和一氧化氮--释放，它们是从哪些神经细胞释放出来的，以及它们对哪些目标神经细胞起作用。最重要的是，它们在这些靶细胞中触发了哪些生化反应，从而如此深刻地改变了蝗虫的行为？为了找出答案，我们将研究蝗虫变化时大脑化学成分的变化。阻止这些变化的药物也能防止蝗虫变得群居吗？我们还需要问，这样的生化过程是否足以改变行为，或者是否有必要开启或关闭基因。我们的第二个目标是了解神经细胞特性的差异以及它们之间的联系如何导致独居和群居蝗虫行为的改变。为了做到这一点，我们将利用这样一个事实，即昆虫有许多巨大的、可识别的神经元，可以从许多个体中记录下来。我们专注于一种识别的视觉神经细胞，它对与蝗虫相撞的物体做出反应。我们将分析这种细胞与控制翅膀和后腿的运动神经细胞的连接，并确定它们是在相变过程中以同样的方式进行修改，还是独立调整以适应特定的行为。另一个检测翅膀运动的神经细胞建立的连接的强度是否像视觉神经细胞一样被改变了？群居的蝗虫白天飞行，独居的蝗虫大多在晚上飞行。我们希望知道视觉系统的反应是如何适应这两个阶段的昼夜活动的，以及中枢神经系统的内部时钟是否会改变眼睛和视觉神经元对白天或黄昏开始的预期的敏感度。我们的第三个目标是分析独居和群居蝗虫的衰老速度，以及这如何影响神经细胞的功能。独居蝗虫成虫寿命比群居蝗虫寿命长45%，这使得我们可以通过改变蝗虫的阶段来控制蝗虫的衰老速度。活细胞积累与衰老相关的损伤的分解产物，称为脂褐素，形成颗粒，可以在显微镜下看到，使我们能够测量单个神经细胞的衰老速度。此外，一氧化氮，一种在相变过程中大量产生的物质，会对细胞造成老年性损害。我们将确定相变过程本身是否会导致加速衰老，而不是像已经处于群居阶段的蝗虫那样加速衰老。我们将从上面详细描述的相同的运动神经细胞中记录下来，以分析衰老如何改变神经细胞对传入信号的反应方式以及与其他神经细胞的交流方式。

Many animals undergo profound changes in form and function in response to fluctuating environmental conditions, of which the Desert Locust is a notorious example. It can change reversibly from a cryptic solitary living form to a swarming form that occasionally aggregates in vast numbers to devastating effect. These two forms, the solitarious and gregarious phases, differ considerably in appearance, physiology and behaviour. Since a major goal of Neuroscience is to understand how changes in behaviour are underpinned by modifications of the nervous system, phase change in locusts is a powerful model system in which to pursue this goal. Our aims in this research proposal are three-fold. The first is to understand how signals provided by other locusts act on the central nervous system of solitarious locusts and start to modify the connections between nerve cells so that a previously solitarious locust will behave like a gregarious locust within 4 hours of first contact. We already know that touch signals provided by other locusts drive behavioural gregarization and that these signals trigger the release of two substances in the central nervous system. We wish to know how touch stimuli cause these substances, serotonin and nitric oxide, to be released, which nerve cells they are released from and on which target nerve cells they act. Most importantly, what biochemical reactions do they trigger in these target cells to so profoundly change the locust's behaviour? To find out we will study the changes in brain chemistry that occur as locusts change phase. Can drugs that prevent these changes also prevent a locust from turning gregarious? We also need to ask whether such biochemical processes suffice to switch the behaviour or whether it is necessary to switch genes on or off. Our second aim is to understand how differences in the properties of nerves cells and the connections between them lead to altered behaviours in solitarious and gregarious locusts. To do this we will exploit the fact that insects have many large and identifiable neurons that can be recorded from in many individuals. We have focussed on an identified visual nerve cell that responds to objects on collision course with the locust. We will analyse the connections of this cell to motor nerve cells that control the wings and hind leg and determine whether they are modified in the same way during phase change or if they are independently adjusted to suit particular behaviours. Are the strengths of connections made by another nerve cell that detects wing movements modified in a similar way as the visual nerve cell? Gregarious locusts fly by day and solitarious locusts mostly at night. We wish to know how the responses of the visual system are adjusted to the day- and night-time activities of the two phases and whether an internal clock in the central nervous system changes the sensitivity of the eyes and visual interneurones in anticipation of the onset of daylight or dusk. Our third aim is to analyse the ageing rate of solitarious and gregarious locusts and how this affects the function of nerve cells. Solitarious locusts live 45% longer as adults than gregarious allowing us to manipulate the rate of ageing of locusts by changing their phase. Living cells accumulate the breakdown products of ageing-related damage, called lipofuscin, into granules that can be seen under a microscope allowing us to measure the rate of ageing in individual nerve cells. Furthermore, nitric oxide, one of the substances that are produced in abundance during phase change causes ageing-type damage to cells. We will determine whether the process of phase-change itself causes accelerated ageing over and above that expected from a locust already being in a gregarious phase. We will record from the same identified motor nerve cells detailed above to analyse how ageing changes the way in which a nerve cell responds to incoming signals and communicates with other nerve cells.