Presynaptic plasticity in the control of mushroom body memory formation

对于突触性能的动态变化（“可塑性”）如何与电路操作交叉，从而定义行为状态，我们的理解仍然存在根本性的差距。果蝇蘑菇体（Drosophila mushroom body， MB）提供了一种分子/细胞与行为层面的综合分析，研究了厌恶嗅觉记忆的形成和巩固。我们在上一个资助期分析了稳态突触前可塑性（“precale”）在MB凯尼恩细胞（KCs）记忆形成中的作用，我们之前发现这种可塑性形式负责在10分钟内在结构/功能上重塑突触前活跃区。我们发现kc特异性的发育后执行突触和驱动precale的调节蛋白的敲低不会影响短期记忆，但会强烈干扰中期记忆的提取。尽管如此，我们仍然缺乏对MB电路中这种可塑性形式的时空作用的理解。我们现在建议通过限制所分析的KC神经元子集并采用简单的学习策略来降低我们分析的细胞和行为复杂性。此外，我们努力直接可视化发生在KC突触上的可塑性过程，并在此基础上扩展我们关于协调precale的分子/细胞生物学机制的知识。因此，我们希望能够了解到电路优化是如何利用稳态可塑性来实现沿巩固轨迹学习信息的成功电路整合的。

There is still a fundamental gap in our understanding of how dynamic changes of synapse performance (“plasticity”) intersect with circuit operation and, consequently, define behavioral states. The Drosophila mushroom body (MB) offers for an integrated analysis connecting the molecular/cellular with the behavioral level, here aversive olfactory memory formation and consolidation. We in the last funding period analyzed the role of homeostatic presynaptic plasticity (“PreScale”) for memory formation in the MB Kenyon cells (KCs), a plasticity form we previously found responsible to structurally/functionally remodel presynaptic active zones over 10s of minutes. We found that KC-specific post-developmental knockdown of executory synaptic and regulatory proteins driving PreScale did not affect short-term memory, but robustly interfered with the retrieval of mid-term memories. Still, we still lack an understanding of the spatio-temporal action of this plasticity form within the MB circuitry. We now suggest to reduce the cellular and behavioral complexity of our analysis by restricting the KC neuron subsets analyzed and involve simple learning strategies. Moreover, we strive to directly visualize the plasticity processes taken place at KC synapses, and in connection extend our knowledge concerning the molecular/cell-biological machinery orchestrating PreScale. In result, we hope to arrive at a picture of how circuit refinement uses homeostatic plasticity to allow for the successful circuit integration of to be learned information along the consolidation trajectory.