Behavioural, Optogenetic and Genetic Dissection of Simple Forms of Plasticity

动物生活在不断变化的环境中，如果它们想要生存，就必须改变自己的行为来应对环境的变化。行为可塑性的最简单形式是：感觉适应、习惯化、去习惯化和敏感化。感觉适应是当感官感受器停止对刺激(感觉疲劳)做出反应时，习惯化是当动物对似乎不能预测任何好或坏的重复刺激的反应减少。习惯化与适应的区别有两个方面：1)施加新的或有害的强刺激后，习惯化可以立即逆转，这一过程称为去习惯化；2)习惯化根据习惯化过程中刺激的速度而不同地自发恢复；这个速度与从疲劳中恢复的预测相反。敏化被认为是一种生物体范围的唤醒，在检测到刺激或威胁刺激后增加所有反应。通常，这些简单的过程在不同的生物体中被孤立地研究，并且在一个或多个生物体中发现了其中一些过程的一些机械性的见解。Groves和Thompson(1970年)的双过程理论使用了来自广泛生物体的行为数据来假设习惯化发生在行为的局部S-R回路中，而敏化和去习服(他们认为本质上是相同的过程)发生在整个有机体中，并反映了动物状态系统的变化。习惯化的定义特征之一是它不是感官适应。然而，这是真的吗？关于适应是否在习惯化中起作用，目前还没有系统的研究。我们正在使用线虫线虫，一种只有302个神经元(脑细胞)的动物，我们有一个完整的接线图，一个能够接受许多尖端基因工程工具的测序基因组，以了解调节感觉适应、习惯化、去栖息化和敏化的基因。我的实验室已经研究线虫行为的遗传基础超过25年了，我们在这一领域的重要问题上的工具、技术和知识方面拥有开展这项研究的经验。我的NSERC资助的首要目标是系统地研究遗传模式生物线虫中这四种简单形式的可塑性，以了解这些行为现象背后的机制，并了解它们之间的关系，以便深入了解它们是如何整合在一起，以产生适应条件变化的刺激条件的行为。由于这些简单的可塑性形式在动物身上一直存在，我们的结果也将得出一般原则，所有研究学习和记忆的研究人员都应该考虑这些原则。

Animals live in constantly changing environments and they must change their behaviour in response to changes in the environment if they are going to survive. The simplest forms of behavioural plasticity are: sensory adaptation, habituation, dishabituation and sensitization. Sensory adaptation is when the sensory receptors stop responding to stimuli (sensory fatigue), habituation is when animals decrease responding to a repeated stimulus that does not seem to predict anything good or bad. Habituation is distinguished from adaption in two ways: 1) it can be reversed immediately after applying a strong novel or noxious stimulus, a procedure called dishabituation, and 2) habituation spontaneously recovers differently depending on the rate of stimulation during habituation; this rate is the opposite of what recovery from fatigue would predict. Sensitization is thought of as an organism-wide arousal that increases all responses after detection of an exciting or threatening stimulus. Usually, these simple processes have been studied in isolation in different organisms and some mechanistic insights have been uncovered for some of these processes in one or more organisms. The Dual Process Theory by Groves and Thompson (1970) used behavioural data from a broad range of organisms to hypothesize that habituation occurs in the local S-R circuit for the behaviour, while sensitization and dishabituation (they suggested were essentially the same process) occur organism-wide and reflect a change in the state system of the animal. One of the defining characteristics of habituation is that it is not sensory adaptation. however, is that true? There have been no systematic investigations into whether adaptation can play a role in habituation. We are using the nematode C. elegans, an animal with only 302 neurons (brain cells) for which we have a complete wiring diagram, a sequenced genome that is amenable to many cutting-edge genetic engineering tools, to understand the genes that mediate sensory adaptation, habituation, dishabituation, and sensitization. My laboratory has been studying the genetic basis of behaviour in C. elegans for more than 25 years and we have experience with the tools, the technology and knowledge of the important questions in this area to carry out this research. The overarching goal of my NSERC grant is to systematically investigate these 4 simple forms of plasticity in the genetic model organism C. elegans in order to understand the mechanisms underlying these behavioural phenomena, and understand the relationships between them in order to gain insight into how they are integrated to produce adaptive behaviour in response to changing stimulus conditions. Because these simple forms of plasticity are going on in animals all of the time, our results will also result in general principles that should be considered by all researchers studying learning and memory.