How does the amnesiac gene product aid memory?

描述（由申请人提供）：我们都有记忆，我们都知道，我们忘记了一些关键的-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，它有一个相对简单的大脑，它是服从遗传方法。 这种应用程序的重点是果蝇健忘症（amn）突变。变异果蝇的记忆力很差。amn基因编码一个假定的前原神经肽，与哺乳动物神经调节剂垂体腺苷酸环化酶激活肽（PACAP）具有同源性。我们将采取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.识别记忆所需的AMN神经肽片段。所有假定的前体片段都是记忆所必需的吗？如果不是，哪些片段是？PACAP同源性重要吗？ 2.识别记忆相关AMN受体。预测的果蝇PACAP型受体参与记忆吗？它们是AMN受体吗？ 3.描述AMN影响的细胞内信号级联反应。我们在PACAP信号的一个新的潜在成分中发现了一个突变体-一种受体酪氨酸激酶，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信号中。 与果蝇学习有关的基因与哺乳动物的基因功能相似。此外，越来越清楚的是，人类滥用的药物在相关的神经回路中参与了类似学习的突触可塑性。因此，我们在果蝇学习中发现的分子最终可能对人类记忆和药物康复治疗有用。

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.