Neurogenetic Analysis of a Visual Working Memory in Drosophila melanogaster

除了简单的反射，动物的适应性行为是不可想象的，如果它们没有记住外部刺激，自己的行为及其后果的能力。昆虫在一次旅行中采用不同的策略，以便找到巢穴或只是它们的起点。例如，自身位置可以相对于参考点存储，并且在地标离开视野的情况下进行独特地更新。事实上，我们已经在遗传模式生物黑腹果蝇（Drosophila melanogaster）中发现了这种视觉定向的工作记忆。通过对果蝇脑结构突变体椭球体开放（ebo）的分析，我们发现果蝇中枢脑中的椭球体是方位记忆的相关结构。对ebo突变体的分子分析表明，转录激活因子血清反应因子（dSRF）的果蝇直系同源物对于成年椭圆体中的功能性工作记忆是必不可少的。此外，cGMP调节蛋白激酶（PKG）编码的觅食和S6激酶II（RSK 2）编码的无知都是必不可少的一个共同的途径在果蝇椭圆体的环神经元。遗传相互作用的研究表明，觅食PKG积极调节无知激酶的活性。本基金申请的目的是利用遗传学、神经解剖学和行为生理学的方法详细了解果蝇的视觉定向记忆。我们的目标是解开完整的信号转导途径，其中两种蛋白激酶共同发挥作用。初步结果表明，转录激活因子CREB（cAMP反应元件结合蛋白）及其靶基因形成该途径的终点。对于神经元来说，能够保持这种短短几秒钟的记忆，相应的基因表达似乎是不可避免的;它的瞬时底物还有待确定。此外，我们的目标是了解转录因子dSRF和PKG-RSK 2信号通路之间的相互作用。总体目标是揭示学习的基本分子机制，特别是那些短暂的工作记忆，需要建立一个方向记忆从急性视觉信息。我们希望找到，至少部分，新的和替代的原则和信号通路相比，那些管理嗅觉条件反射与其短期，中期和长期的记忆形式。

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.