Role of acetylcholine in Drosophila memory

描述(申请人提供)：记忆是人类日常生活中必不可少的组成部分。神经退行性疾病，如阿尔茨海默氏症，削弱了我们的记忆能力，极大地影响了美国人的生活。据估计，到2050年，将有超过1300万美国人患有这种疾病(Hebert等人，2003年)，这使得阿尔茨海默氏症和其他健忘症成为紧迫的医疗问题。果蝇是学习和记忆研究的优秀模式生物，在这种生物中已经发现了损害记忆的单基因突变。健忘症基因编码一种与哺乳动物PACAP同源的神经肽，在背侧配对内侧(DPM)神经元中高度表达。我的初步证据有力地表明，DPM神经元也产生经典的递质乙酰胆碱(ACh)。经典神经递质在果蝇记忆中的作用还没有研究。这一建议利用果蝇强大的遗传学来研究ACh在学习和记忆中的作用。这一知识应该会为理解经典神经递质和神经肽如何共同影响记忆提供重要的见解。

DESCRIPTION (provided by applicant): Memory is an essential component of every day human life. Neurodegenerative diseases, such as Alzheimer's, that impair our ability to remember drastically affect the lives of Americans. It is estimated that by the year 2050, over 13 million Americans will suffer from this disease (Hebert et al., 2003), making Alzheimer's and other diseases of forgetfulness urgent medical issues. The fruit fly Drosophila melanogaster is an excellent model organism for learning and memory study and single gene mutations that impair memory have been identified in this organism. The amnesiac gene, which encodes for a putative neuropeptide with homology to mammalian PACAP, is highly expressed in Dorsal Paired Medial (DPM) neurons. My preliminary evidence strongly suggests that DPM neurons also produce the classical transmitter acetylcholine (ACh). The role of classical neurotransmitters in Drosophila memory has not been studied. This proposal utilizes the powerful genetics available in Drosophila to examine the role of ACh in learning and memory. This knowledge should provide important insight into understanding how classical neurotransmitters and neuropeptides work together to affect memory.