Behavioural, Optogenetic and Genetic Dissection of Simple Forms of Plasticity

简单形式可塑性的行为、光遗传学和遗传学剖析

• 批准号: RGPIN-2019-05558
• 负责人: Rankin, Catharine
• 金额: $ 4.01万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=714585
• 关键词: Behavioural; Optogenetic; Genetic; Dissection; Simple

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.

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。行为可塑性最简单的形式是：感觉适应、习惯化、不习惯化和敏感化。感觉适应是指感觉受体停止对刺激做出反应（感觉疲劳），习惯化是指动物对反复出现的似乎无法预测好坏的刺激反应减少。习惯化与适应的区别有两个方面：1)在施加强烈的新刺激或有害刺激后，习惯化可以立即逆转，这一过程被称为“不习惯化”；2)在习惯化过程中，根据刺激的频率，习惯化会以不同的方式自动恢复；这一速度与疲劳恢复的预期相反。敏化被认为是一种生物体的觉醒，在检测到令人兴奋或威胁的刺激后，会增加所有的反应。通常，这些简单的过程是在不同的生物中单独研究的，并且已经发现了其中一些过程在一个或多个生物中的一些机制。Groves和Thompson（1970）的双过程理论（Dual Process Theory）利用来自广泛生物的行为数据，假设习惯化发生在行为的局部S-R回路中，而敏化和不习惯化（他们认为本质上是相同的过程）发生在整个生物体内，反映了动物状态系统的变化。习惯化的一个决定性特征是它不是感官适应，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。我们正在使用秀丽隐杆线虫，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，一个测序的基因组，可以适用于许多尖端的基因工程工具，来了解介导感觉适应，习惯化，不习惯化和敏感化的基因。我的实验室已经研究秀丽隐杆线虫行为的遗传基础超过25年，我们在工具、技术和该领域重要问题的知识方面有经验，可以开展这项研究。我的NSERC基金的首要目标是系统地研究遗传模式生物秀丽隐杆线虫中这4种简单的可塑性形式，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，产生适应行为，以应对不断变化的刺激条件。因为这些简单的可塑性形式一直在动物身上发生，我们的研究结果也将得出所有研究学习和记忆的研究人员都应该考虑的一般原则。