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经验如何重新权衡信息流 穿过大脑回路这涉及在神经元的不同区域发生的可塑性（即，亚细胞 区室化）。我们的初步数据揭示了神经元内信号的区室化， 编码嗅觉记忆，并进一步发现学习驱动空间广泛的Ca2+升高。这 表明，在学习过程中，多个信号在不同的空间尺度上被整合，以调节 分区可塑性在这里，我们将测试如何划分可塑性驱动的合奏， 神经系统中跨多个空间尺度的变化，导致连贯的动作选择。 我们将测试亚细胞水平的突触前可塑性分区机制，使用 黑腹果蝇的遗传上强大的、高度易控制的神经系统。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 这是基本决策过程的中介。我们将使用这个系统作为一个测试平台， 在分子水平上的区室化可塑性机制，检查细胞整合和突触 可塑性，并探讨这些过程如何通过离散电路上的动作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的，以及在大脑疾病中是如何被破坏的， 记忆障碍治疗的合理设计。目前的研究结果将为以下方面提供指导 未来的研究，以分子生物学的记忆形成跨多种模式生物（包括 哺乳动物），作为关键分子的功能，细胞机制，细胞区室化和突触 功能，电路图案和计算原语在物种之间是保守的，在物种之间是至关重要的。 多种电路和存储器类型。该项目将支持我们理解记忆的长期目标 下至单细胞水平，有助于合理开发所需的知识基础， 治疗记忆障碍的新方法

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.