How does the amnesiac gene product aid memory?

失忆基因产物如何帮助记忆？

• 批准号: 7152540
• 负责人: Scott Waddell
• 金额: $ 30.53万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-12-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7152540
• 关键词: Address; Adenylate Cyclase; Adult; Affect; Behavioral Genetics; Binding; Biological Models; Brain; Cyclic AMP; Data; Defect; Development; Double-Stranded RNA; Drosophila genus; Enhancers; G-Protein-Coupled Receptors; GTP-Binding Proteins; Genes; Genetic; Goals; Homologous Gene; Human; Knockout Mice; Lead; Learning; Ligands; Localized; Mammals; Mediating; Memory; Molecular; Molecular Genetics; Mushroom Bodies; Mutagenesis; N-amyl-N-methylnitrosamine; Nervous system structure; Neuromodulator; Neurons; Neuropeptides; Neurotrophic Tyrosine Kinase Receptor Type 2; Pattern; Peptide Receptor; Peptide Signal Sequences; Peptides; Pharmaceutical Preparations; Pharmacology; Phosphorus; Pituitary Gland; Process; Proteins; Receptor Gene; Receptor Protein-Tyrosine Kinases; Receptor Tyrosine Kinase Gene; Rehabilitation therapy; Reporting; Role; Rutabaga; Second Messenger Systems; Signal Transduction; Synaptic plasticity; Testing; conditioned fear; drug rehabilitation; extracellular; fly; forgetting; gene function; long term memory; memory encoding; mutant; neural circuit; phosphoric diester hydrolase; pituitary adenylate cyclase activating polypeptide; receptor; receptor expression; receptor function; research study

DESCRIPTION (provided by applicant): We all have memories and we all know that we forget some of the crucial ones - especially as we grow older. Our long-term objective is to understand how a brain encodes memory at the molecular and cellular level. We use the fruit fly Drosophila as our model system because it can learn, it has a relatively simple brain and it is amenable to a genetic approach. This application focuses on the Drosophila amnesiac (amn) mutant. Mutant amn flies have poor memory. The amn gene encodes a putative preproneuropeptide with homology to the mammalian neuromodulator pituitary adenylyl cyclase activating peptide (PACAP). We will take molecular genetic and behavioral approaches to understand the role of amn in memory. Our specific aims are: 1. Identify the AMN neuropeptide fragment(s) that are required for memory. Are all the putative fragments of the precursor required for memory and if not, which ones are? Is the PACAP homology important? 2, Identify the memory-relevant AMN receptor(s). Are the predicted fly PACAP-type receptors involved in memory? Are they the AMN receptor(s)? 3. Delineate the intracellular signaling cascade affected by AMN. We have a mutant in a new potential component of PACAP signaling - a receptor tyrosine kinase, off-track. We will analyze the involvement of off-track in learning and more specifically, in AMN signaling. The genes involved in Drosophila learning have related mammalian genes that function similarly. Furthermore, it is becoming increasingly clear that learning-like synaptic plasticity is engaged- in the relevant neural circuits - by drugs of human abuse. Therefore molecules we identify in Drosophila learning may ultimately be useful in human mnemonic and drug rehabilitation therapy.

描述(由申请人提供)：我们都有记忆，我们都知道我们会忘记一些关键的记忆--特别是随着年龄的增长。我们的长期目标是了解大脑如何在分子和细胞水平上编码记忆。我们使用果蝇作为我们的模型系统，因为它可以学习，它的大脑相对简单，而且它服从遗传方法。 这项应用主要针对果蝇失忆(Amn)突变体。突变的Amn苍蝇记忆力很差。Amn基因编码一种可能的前神经肽，与哺乳动物神经调节剂垂体腺苷环化酶激活肽(PACAP)同源。我们将采用分子遗传学和行为学的方法来了解AMN在记忆中的作用。我们的具体目标是： 1.确定记忆所需的AMN神经肽片段(S)。所有假定的前体片段都是记忆所必需的吗？如果不是，哪些是？PACAP同源性重要吗？ 2、确定与记忆相关的AMN受体(S)。预测的苍蝇PACAP型受体与记忆有关吗？它们是AMN受体(S)吗？ 3.研究AMN对细胞内信号转导的影响。我们在PACAP信号的一个新的潜在成分-受体酪氨酸激酶中有一个突变，偏离了轨道。我们将分析偏离轨道在学习中的参与，更具体地说，在AMN信号传递中。 参与果蝇学习的基因都有相关的哺乳动物基因，功能相似。此外，越来越清楚的是，人类滥用的药物参与了类似学习的突触可塑性--参与了相关的神经回路。因此，我们在果蝇学习中识别的分子最终可能在人类助记和药物康复治疗中有用。