GENETIC ANALYSIS OF LEARNING AND MEMORY IN DROSOPHILA

果蝇学习和记忆的遗传分析

• 批准号: 3285878
• 负责人: WILLIAM G QUINN
• 金额: $ 20.23万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-07-01 至 1989-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3285878
• 关键词: affinity labeling; behavioral genetics; biochemical evolution; cyclic AMP; cyclic GMP; drug adverse effect; ethology; gel electrophoresis; gene dosage; gene expression; genetic mapping; heart; larva; memory; molecular psychobiology; neurons; neurotransmitter metabolism; neurotransmitters; nontherapeutic iontophoresis; phosphodiesterase inhibitors; phosphorylation; physiology; protein kinase; purine /pyrimidine metabolism; radioimmunoassay; serotonin; short term memory; synapses; synthetic enzyme; temperature sensitive mutant

Work with Drosophila learning mutants has yielded insights on the biochemical mechanism underlying learning and memory. Of the six learning-deficient mutants isolated to date, four show well defined alterations in monoamine transmitter metabolism, or in cyclic AMP metabolism. In general, mutations which affect monoamines tend primarily to effect learning acqusition; while those which affect cAMP metabolism tend to affect short term memory retention after training. For two mutations that affect learning - dunce and Dopa decarboxylase - the primary metabolic lesions has been identified using gene-dosage studies and temperature-sensitive alleles. This needs to be done with our other mutants with well defined biochemical effects - turnip (affects serotonin receptor binding activity); rutabaga (affects calcium-activated adenylate cyclase) and radish (affects protein phosphorylation). We will try to do this (i) by orthodox biochemical experiments on the relevant metabolic lesions; (ii) by better genetic mapping to ensure that the biochemical lesions co-map with the learning defect; (iii) by gene-dosage studies and (iv) by isolating new mutant alleles, including temperature-sensitive ones. Using segmental-aneuploid screens, we will also try to map and obtain mutants in other proteins on the learning-related metabolic pathway - in three monoamine synthetic enzymes, in the Ns protein, and in cAMP dependent protein kinase. We will continue our work on the larval heart, which appears to alter its beat rate by the same serotonin-cAMP system implicated in learning. We will also continue our behavioral work, seeking to refine the correlation between biochemistry and behavior for temperature-sensitive dunce and rutabaga mutants.

与果蝇学习突变体合作已经对 学习和记忆的基础生化机制。 六个 学习缺陷的突变体迄今为止孤立，四个显示明确定义 单胺发射机代谢或环状AMP的改变 代谢。 通常，影响单胺的突变主要倾向于 实现学习acqusition；而那些影响营地代谢的人 训练后倾向于影响短期记忆的保留。 对于影响学习的两个突变 - 邓ce和dopa脱羧酶 - 已经使用基因剂量研究确定了原发性代谢病变， 温度敏感的等位基因。 这需要与我们的对方一起完成 具有明确定义的生化作用的突变体 - 萝卜（影响5-羟色胺 受体结合活性）； rutabaga（影响钙激活的腺苷酸盐 环化酶）和萝卜（影响蛋白质磷酸化）。 我们将尝试做 这（i）由相关代谢的正统生化实验 病变； （ii）通过更好的遗传图来确保生化 病变与学习缺陷共同地图； （iii）通过基因剂量研究和 （iv）通过隔离新的突变等位基因，包括温度敏感 一个。 使用节段 - 倍倍屏屏幕，我们还将尝试映射和 在与学习相关的代谢途径上获得其他蛋白质中的突变体 - 在三种单胺合成酶中，在NS蛋白和cAMP中 依赖性蛋白激酶。 我们将继续在幼虫心上的工作，这似乎改变了它 与学习有关的相同的5-羟色胺训练训练训练训练训练系统的节拍率。 我们 还将继续我们的行为工作，试图完善相关性 在温度敏感的笨蛋的生物化学和行为之间 rutabaga突变体。