Mechanisms of compartmentalized plasticity in learning and memory

项目摘要 神经科学研究的一个主要目标是了解体验如何重新衡量信息流。 横跨大脑回路。这涉及到发生在神经元不同区域(即亚细胞)的可塑性 分隔化)。我们的初步数据揭示了神经元内信号的区隔 对嗅觉记忆进行编码，并进一步发现学习推动了空间上广泛的钙升高。这 提示在学习事件期间，多个信号在不同的空间尺度上被整合以进行调制 划分的可塑性。在这里，我们将测试划分的可塑性如何驱动 神经系统中多个空间尺度的变化导致一致的动作选择。 我们将测试划分到亚细胞水平的突触前可塑性的机制，使用 黑腹果蝇在遗传上强大的、高度易驯化的神经系统。果蝇 蘑菇体(MB)将嗅觉信息从嗅觉投射神经元传递到下游回路 调解基本的决策过程。我们将使用该系统作为试验床来剖析 分子水平上的可塑性区区化机制，检查细胞整合和突触 可塑性，并探索这些过程如何通过对离散电路的作用来调节行为动作选择 来调节行为。 了解记忆是如何在大脑中编码并在大脑紊乱中被破坏的是 合理设计记忆障碍的治疗方法。本研究的结果将为以下工作提供指导 未来对多个模式生物(包括 哺乳动物)，作为关键分子、细胞机制、细胞区划和突触的功能 函数、电路基元和计算基元在物种之间都是保守的，并且在 多种电路和类型的存储器。该项目将支持我们理解记忆的长期目标 直到单细胞级别，为合理开发所需的知识库做出贡献 记忆力受损的新疗法。

Project Summary A major goal of neuroscience research is to understand how experience reweights the flow of information across brain circuits. This involves plasticity that occurs at across different regions of neurons (i.e., subcellular compartmentalization). Our preliminary data revealed compartmentalization of signaling within neurons that encode olfactory memories, and further found that learning drives spatially broad elevations of Ca2+. This suggests that multiple signals are integrated across different spatial scales during learning events to modulate compartmentalized plasticity. Here we will test how compartmentalized plasticity drives the ensembles of changes across multiple spatial scales in the nervous system that leads to coherent action selection. We will test the mechanisms of compartmentalized presynaptic plasticity down to the subcellular level, using the genetically powerful, highly tractable nervous system of Drosophila melanogaster. The Drosophila mushroom body (MB) carries olfactory information from olfactory projection neurons to downstream circuits that mediate fundamental decision-making processes. We will use this system as a testbed to dissect the mechanisms of compartmentalized plasticity at the molecular levels, examine cellular integration and synaptic plasticity, and probe how these processes modulate behavioral action selection via actions on discrete circuits that modulate behavior. Understanding how memories are encoded in the brain and disrupted in brain disorders is a prerequisite to the rational design of treatments for memory impairment. Results of the present studies will provide guideposts for future research into the molecular biology of memory formation across multiple model organisms (including mammals), as the function of key molecules, cellular mechanisms, cellular compartmentalization and synaptic function, circuit motifs, and computational primitives are both conserved across species and crucial across multiple circuits & types of memory. The project will support our long-term goal of understanding of memory down to the single-cell level, contributing to the knowledge base necessary for the rational development of novel treatments for memory impairment.