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: 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=716412
• 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好理解的多细胞生物（蠕虫C。elegans）-第一个拥有完整的基因组测序和完整的神经连接体图谱。我们过去的工作特点是联想学习和记忆的C。线虫，以味觉和嗅觉作为条件刺激，以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，一个新的学习突变（lrn-2）被克隆出来，并显示是一个突变，特别是在scd-2，一个受体酪氨酸激酶。最令人惊讶的是，野生型scd-2需要在一个中间神经元（AIA）的整合两个感官刺激，以控制行为，但在一个单独的神经元（NSM）的长期联想记忆。此外，我们已经证明了蠕虫的高阶联想学习过程（Kamin阻塞和场合设置），有些人可能会想象只有在更复杂的动物中才存在。事实上，我们对蠕虫突变体的研究表明，卡明阻断联想学习可能是由于干扰记忆回忆而不是记忆储存。 在我们最可靠的学习和记忆试验中，苯甲醛的气味和没有细菌食物的单一配对产生了对通常偏好的苯甲醛的学习回避;然后持续几个小时的记忆。我们建议专注于这项试验，以揭示特定的神经元和分子介导的条件刺激（目标1），非条件刺激（目标2），以及它们的协会和随后的存储所产生的记忆（目标3）的影响。