Mutational Analyses of Learning and Memory

学习和记忆的突变分析

• 批准号: RGPIN-2020-04339
• 负责人: vanderKooy, Derek
• 金额: $ 3.06万
• 依托单位: University of Toronto
• 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=761252
• 关键词: Mutational; Analyses; Learning; Memory

Our goal is to use the power and specificity of modern mutational molecular genetics to reveal the component processes of learning and memory. Our research employs the best-understood multicellular organism (the worm C. elegans) - the first to have a completely sequenced genome and a fully mapped neural connectome. Our past work has characterized associative learning and memory in C. elegans, using tastes and smells as conditioned stimuli and the presence or absence of food as unconditioned stimuli. Screens of mutant worms have revealed novel genes involved in worm learning and memory. For example, one novel learning mutation discovered (lrn-2) was cloned and shown to be a mutation specifically in scd-2, a receptor tyrosine kinase. Most surprising, wild type scd-2 is required in one interneuron (AIA) for the integration of two sensory stimuli to control behaviour but in a separate neuron (NSM) for longer-term associative memory. Moreover, we have demonstrated higher order associative learning processes in worms (Kamin blocking and occasion setting) that some might have imagined were present only in more complex animals. Indeed, our studies of worm mutants have revealed that Kamin blocking of associative learning may be due to interference with memory recall rather than memory storage. In our most robust assay for learning and memory, a single pairing of the smell of benzaldehyde and the absence of bacterial food produces a learned avoidance of the normally preferred benzaldehyde; a memory which then lasts for a few hours. We propose to focus on this assay in order to reveal the specific neurons and molecules mediating the effects of the conditioned stimulus (Objective 1), the unconditioned stimulus (Objective 2), and their association and subsequent storage of the memory produced (Objective 3).

我们的目标是利用现代突变分子遗传学的力量和特异性来揭示学习和记忆的组成过程。我们的研究采用了最了解的多细胞生物（秀丽隐杆线虫）——第一个拥有完全测序的基因组和完全绘制的神经连接组。我们过去的工作描述了秀丽隐杆线虫的联想学习和记忆，将味道和气味作为条件刺激，将食物的存在或不存在作为非条件刺激。突变蠕虫的筛选揭示了与蠕虫学习和记忆有关的新基因。例如，一种新的学习突变（lrn-2）被克隆，并被证明是酪氨酸激酶受体scd-2的突变。最令人惊讶的是，野生型scd-2需要在一个中间神经元（AIA）中整合两种感觉刺激来控制行为，但需要在一个单独的神经元（NSM）中进行长期联想记忆。此外，我们已经证明了蠕虫的高阶联想学习过程（卡明阻塞和场合设置），有些人可能认为这只存在于更复杂的动物中。事实上，我们对蠕虫突变体的研究表明，联想学习的卡明阻塞可能是由于对记忆回忆的干扰，而不是对记忆存储的干扰。在我们最强大的学习和记忆实验中，苯甲醛的气味和没有细菌食物的单一配对产生了对通常首选苯甲醛的学习回避；这种记忆会持续几个小时。为了揭示条件刺激（目标1）、非条件刺激（目标2）以及它们之间的关联和随后产生的记忆存储（目标3），我们建议将重点放在这一实验上。