Molecular genetics of neural development and plasticity of the learning and memory centers in Drosophila

蘑菇体是果蝇嗅觉联想学习和基本认知功能的中枢。为了系统地阐明MB中优先表达的基因，我们使用果蝇全基因组微阵列调查了MB转录本，并选择了102个在MB切除的大脑中表现出最一致的表达水平降低的基因。通过原位杂交对幼虫和成虫体内表达模式的分析表明，大多数基因的MB优先表达模式是在变态过程中建立的。此外，针对MB神经元发育的RNA干扰导致许多已鉴定的基因出现轻微到强烈的结构缺陷。我们还开发了一种新的范例，幼虫通过单一气味和积极的味觉强化物蔗糖进行联想学习。有趣的是，食欲条件作用产生的幼虫记忆持续中期，并依赖于失忆症和cAMP反应元件结合蛋白（CREB）。此外，幼虫MB神经元的突触输出是检索所必需的，而不是获取和保留幼虫的记忆，包括creb依赖的成分。这些结果对控制MB神经元分化和重塑的基因库以及在学习和记忆过程中MB神经元突触可塑性中起作用的神经因子库提供了新的见解。

Mushroom bodies (MBs) are the centers for olfactory associative learning and elementary cognitive functions in the Drosophila brain. As a way to systematically elucidate the genes preferentially expressed in MBs, we surveyed MB transcripts using a Drosophila whole-genome microarray and selected 102 genes that exhibited a most consistent reduction of expression levels in MB ablated brains. In vivo analyses of larval and adult expression patterns by in situ hybridization reveal that the preferential MB expression patterns for most of the genes are established during metamorphosis. Moreover, RNA interference targeted developmentally to the MB neurons resulted in mild to strong structural defects for many of the identified genes. We have also developed a novel paradigm of larval associative learning with a single odor and a positive gustatory reinforcer, sucrose. Intriguingly, larval memory produced by the appetitive conditioning lasts medium-term and depends on both amnesiac and cAMP response element-binding protein (CREB). Moreover, synaptic output of larval MB neurons is required for retrieval but not for acquisition and retention of the larval memory including the CREB-dependent component. These results provide novel insights into the repertoire of the genes that control differentiation and remodeling of the MB neurons as well as the repertoire of neural factors that have functions in the synaptic plasticity of MB neurons during learning and memory.