果蝇蘑菇体亚型之间的细胞通讯对记忆的调控及其机制

Memory is the foundation of all cognitive function. Many neurological disorders cause memory deficits, such as Alzheimer's Disease and Post-Trauma Stress Disorders. Studies in animal models such as Drosophila are the key for our understanding of the molecular and neural circuit mechanisms underlying memory process. Mushroom body (MB) is a structure in the Drosophila brain that is essential for olfactory memory. The MB is composed of 3 principle cell types, including α/β, α'/β' and γ neurons. The applicant's previous studies have led to a model in which aversive memory is exclusively formed in γ neurons and followed by communication between γ and other MB subtypes of neurons to support memory consolidation. We hypothesize that MB neurons communicate with each other via gap junctions or neuropeptides to support memory consolidation. To test this hypothesis, I will use transgenic RNAi to knock down each innexin and neuropeptide genes in the genome. For each gene that is required for normal memory performance, I will use a combination of molecular, cellular and behavioral techniques to further define its role in each MB lobe during memory consolidation. This project will deepen our understanding of the circuit mechanisms of memory consolidation in the MB sub-structure level.

记忆是所有认知功能的基础，很多神经系统病变都与记忆障碍有关，比如阿尔茨海默病和创伤后应激障碍等。利用包括果蝇在内的动物模型深入研究其分子和神经环路机制是理解记忆的关键。果蝇的嗅觉记忆神经中枢是蘑菇体。蘑菇体神经元分为三个亚型，α/β神经元、α'/β'神经元和γ神经元。基于申请人的前期研究，我们认为记忆首先在γ神经元中习得，然后在α/β神经元中固化成长时程记忆。这意味着记忆的固化需要蘑菇体神经元之间进行信息交流。我们推测这种细胞通讯（即信息交流）是由缝隙连接或神经多肽所介导的。本项目将利用转基因RNAi技术对果蝇基因组中所有的缝隙连接和神经多肽基因进行筛选，以发现在蘑菇体中影响嗅觉记忆的细胞通讯基因。并将在行为、分子和细胞等多个水平上阐明这些基因在不同蘑菇体亚型中调控记忆的机制。本项目的顺利实施将加深我们对蘑菇体亚结构神经环路的了解，为最终理解记忆固化的神经环路机制奠定基础。