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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=764121
• 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，如果它们要生存，它们必须改变自己的行为以应对环境的变化。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。感觉适应是当感觉受体停止对刺激做出反应时（感觉疲劳），习惯化是当动物减少对重复刺激的反应时，似乎不能预测任何好或坏。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，这一过程称为去习惯化; 2）习惯化的自发恢复取决于习惯化过程中刺激的速度;这个速度与疲劳的恢复速度相反。敏化被认为是一种生物体范围内的唤醒，在检测到兴奋或威胁刺激后会增加所有反应。通常，这些简单的过程已经在不同的生物体中被孤立地研究，并且已经在一个或多个生物体中发现了这些过程中的一些机制。格罗夫斯和汤普森（Thompson，1970）的双重过程理论（Dual Process Theory）使用了来自广泛生物体的行为数据，假设习惯化发生在行为的局部S-R回路中，而敏感化和去适应化（他们认为本质上是同一个过程）发生在整个生物体中，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。但是，这是真的吗？对于适应是否在习惯化中发挥作用，还没有系统的研究。我们用线虫C. elegans，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，一个经过测序的基因组，可以用许多尖端的基因工程工具来理解介导感觉适应，习惯化，disabituation和敏化的基因。我的实验室一直在研究C. elegans超过25年，我们有经验的工具，技术和知识的重要问题，在这一领域开展这项研究。我的NSERC基金的首要目标是系统地研究遗传模式生物C中这4种简单形式的可塑性。为了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的，以产生适应性行为，以应对不断变化的刺激条件。因为这些简单形式的可塑性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。