Functional Anatomy of Learning and Memory in Drosophila

描述（由申请人提供）：行为层面的研究表明，在脊椎动物和无脊椎动物物种中，记忆巩固涉及通过几个不同的时间“阶段”处理信息。在解剖学水平上，记忆在许多情况下似乎是在不同的位点之间动态转移的。即使是在相对简单的无脊椎动物大脑中最基本的联想学习形式，也可以依赖于相对较大的神经元网络中的多种机制。该建议的核心是在果蝇中可获得gal4响应温度敏感（和显性阴性）动力蛋白转基因（UAS-Shi/ ts），该基因允许温度依赖性和可逆的神经元功能破坏。这种遗传工具提供了一个独特的机会，可以从功能上绘制神经回路与记忆等复杂行为之间的关系。我们已经使用这种方法来破坏果蝇大脑几个不同亚区域的神经元功能，从而剖析了获取与检索的解剖学要求，以及麻醉敏感与麻醉抵抗记忆的存储。本研究的目标是进一步定义记忆形成、存储和检索的功能电路。

DESCRIPTION (provided by applicant): Studies at the behavioral level reveal that in both vertebrate and invertebrate species, memory consolidation involves processing of information through several distinct temporal "phases". At the anatomical level, memories appear in many cases to be dynamically transferred between distinct loci. Even elemental forms of associative learning in relatively simple invertebrate brains can rely on multiple mechanisms in relatively large networks of neurons. Central to this proposal is the availability in flies of a Gal4-responsive temperature-sensitive (and dominant negative) dynamin transgene (UAS-Shi/ ts), which permits temperature dependent and reversible disruption of neuronal function. This genetic tool provides a unique opportunity to functionally map the relationships between neural circuitry and a complex behavior such as memory. We already have used this method to disrupt neuronal function in several distinct sub-regions of the fly brain, thereby dissecting the anatomical requirements for acquisition versus retrieval as well as for storage of anesthesia-sensitive versus anesthesia-resistant memory. The goal of this proposal is to further define the functional circuitry underlying memory formation, storage and retrieval. The three Specific Aims of this proposal are: 1- "Functional anatomy"- Each of these 11 non-mushroom body Gal4 enhancer lines, as well as the DPM and MB lines, will be used to drive spatially restricted expression of the Gal4-responsive UAS-Shits transgene. Temperature-shift experiments then will be used to transiently disrupt neuronal function in these foci during each temporal phase of memory consolidation. 2- "Anatomical Dissection of Memory Phases" - Functionally relevant Gal4 lines identified in Aim #1 will be combined with the "phase specific" amnesiac and radish mutants. This "double mutant" approach will permit dissection of the anatomical requirements for amnesiac-dependent memory, which is anesthesia sensitive, from radish-dependant (anesthesia resistant) memory. 3- High Resolution Imaging- Confocal imaging will be used to construct a high-resolution anatomical map of GFP reporter expression for each Gal4 transposon line identified as functionally relevant in Specific Aims I and 2. We will take advantage of the economy-of-scale and molecular genetic tools available only in flies to investigate the relationships between temporal and spatial patterns of neural activity and the ongoing consolidation of memories in the brain. While the anatomical wiring diagram of nervous systems appear species specific, the molecular mechanisms and behavioral properties underlying memory within these circuits are remarkably conserved. As a result, an understanding of the "logic" of how information is processed in relatively simple nervous systems can greatly inform future investigations of human cognition.