Neurogenetic Analysis of a Visual Working Memory in Drosophila melanogaster

除了简单的反射，动物的适应行为如果没有记住外部刺激、自己的行为及其后果的能力，是不可想象的。昆虫在一次远足中使用不同的策略，以便找到一个巢或仅仅是它们的起点。例如，可以相对于参考点存储自己的位置，并在地标离开视线的情况下愚蠢地更新。事实上，我们已经在遗传模式生物黑腹果蝇中发现了这样一种视觉定向的工作记忆。通过对脑结构突变体椭球体开放(EBO)的分析，我们发现果蝇中央脑中的椭球体是定向记忆的相关结构。对ebo突变体的分子分析表明，果蝇转录激活因子血清反应因子(DSRF)的同源基因对于成年椭球体的功能性工作记忆是必不可少的。此外，觅食编码的cGMP调节的蛋白激酶(PKG)和NOWANT编码的S6Kinase II(RSK2)都是果蝇椭圆体环状神经元共同通路中必不可少的信号。遗传交互作用研究表明，觅食PKG正向调节无知蛋白激酶的活性。这项资助申请的目标是利用遗传学和神经解剖学以及行为生理学的方法详细了解果蝇的视觉定向记忆。我们的目标是揭开两种蛋白激酶共同作用的完整信号转导途径。第一个结果表明，转录激活因子CREB(cAMP反应元件结合蛋白)及其靶基因形成了该途径的终点。对于神经元来说，各自的基因表达似乎是不可避免的，能够保持这种记忆只有几秒钟；其短暂的底物仍有待确定。此外，我们的目标是了解转录因子dSRF和PKG-RSK2信号通路之间的相互作用。最重要的目标是解开学习的基本分子机制，特别是那些短暂的工作记忆，从敏锐的视觉信息建立定位记忆所需的那些。我们希望至少在一定程度上找到新的和替代的原理和信号通路，与那些管理嗅觉条件作用的短期、中期和长期记忆形式的原理和信号通路相比。

Apart from simple reflexes adaptive behavior of animals is not imaginable without their ability to remember external stimuli, own actions and the consequences thereof. Insects employ different strategies during an excursion in order to find back to a nest or just their starting point. For instance, the own position can be stored in relation to a point of reference and updated idiothetically in cases where a landmark gets out of view. Indeed, we have identified such a working memory for visual orientation in the genetic model organism Drosophila melanogaster. Analysis of the brain structure mutant ellipsoid-body open (ebo) led us to the ellipsoid body in the central brain of Drosophila as the relevant structure for the orientation memory. Molecular analysis of the ebo mutant showed that the Drosophila ortholog of the transcription activator Serum Response Faktor (dSRF) is essential for a functional working memory in the adult ellipsoid body. Moreover, the cGMP regulated protein kinase (PKG) encoded by foraging and the S6 Kinase II (RSK2) encoded by ignorant are both essential in a common pathway in the ring neurons of the Drosophila ellipsoid body. Genetic interaction studies indicate that foraging PKG positively regulates the activity of the ignorant kinase. It is the goal of this grant application to understand the visual orientation memory of Drosophila in detail using genetic and neuroanatomical methods as well as behavioral physiology. We aim to unravel the complete signal transduction pathway in which both protein kinases act together. First results indicate that the transcription activator CREB (cAMP responsive element binding protein) and its target genes form the endpoint of this pathway. The respective gene expression seems inevitable for the neurons to be able to hold this memory of just a few seconds; its transient substrate remains to be identified. In addition, we aim to understand the interaction between the transcription factor dSRF and the PKG-RSK2 signaling pathway. The overarching goal is to unravel the fundamental molecular mechanisms of learning and particularly those of a short-lived working memory, required to establish an orientation memory from acute visual information. We expect to find, at least in part, novel and alternative principles and signaling pathways as compared to those governing olfactory conditioning with its short-, middle-, and long-term memory forms.