Mechanisms of compartmentalized plasticity in learning and memory

学习和记忆的区隔可塑性机制

• 批准号: 10522519
• 负责人: Seth M Tomchik
• 金额: $ 38.88万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10522519
• 关键词: Acetylcholine; Afferent Neurons; Anatomy; Association Learning; Automobile Driving; Axon; Behavior; Behavioral; Brain; Brain Diseases; Butyrates; Cell physiology; Cells; Cyclic AMP; Data; Decision Making; Development; Dissociation; Drosophila genus; Drosophila melanogaster; Endoplasmic Reticulum; Event; Genomics; Goals; Image; Individual; Investigation; Learning; Mammals; Mediating; Memory; Memory Disorders; Memory impairment; Modeling; Molecular; Molecular Biology; Mushroom Bodies; Mutation; Nervous System; Neurons; Neurosciences Research; Odors; Olfactory Learning; Output; Pathway interactions; Pattern; Process; RNA Interference; Reporter; Resolution; Retrieval; Rewards; Role; Route; Sensory; Signal Transduction; Stimulus; Sucrose; Synapses; Synaptic plasticity; System; Testing; behavioral response; experience; experimental study; flexibility; fly; in vivo imaging; insight; knowledge base; memory encoding; model organism; nervous system disorder; neuronal circuitry; neurotransmitter release; novel; postsynaptic; presynaptic; rational design; response; sensor; sensory stimulus; synaptic function; therapy design

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.

项目摘要 神经科学研究的主要目标是了解经验如何重新获得信息流 跨大脑电路。这涉及在神经元不同区域的可塑性（即亚细胞 分隔）。我们的初步数据揭示了神经元内信号传导的分区化， 编码嗅觉记忆，并进一步发现，学习驱动了Ca2+的空间广泛升高。这 表明在学习事件期间，多个信号在不同的空间尺度上集成以调制 隔室塑性。在这里，我们将测试分隔的可塑性如何推动 神经系统中多个空间尺度的变化导致连贯的作用选择。 我们将使用隔室化的前可塑性的机理，直到亚细胞水平 果蝇果蝇的遗传功能强大，高度可触犯的神经系统。果蝇 蘑菇体（MB）将嗅觉信息从嗅觉投影神经元转移到下游电路 调解基本决策过程。我们将使用此系统作为测试台 分子水平上隔室塑性的机制，检查细胞整合和突触 可塑性，并探测这些过程如何通过离散电路调节行为行动选择 这种调节行为。 了解记忆如何在大脑中编码并在脑部疾病中破坏是一种先决条件 用于记忆障碍的治疗方法的理性设计。本研究的结果将为指南提供 对多种模型生物的记忆形成的分子生物学的未来研究（包括 哺乳动物），作为关键分子的功能，细胞机制，细胞隔室化和突触 功能，电路图案和计算基原始物质既保存在物种之间，又有至关重要的 多个电路和内存类型。该项目将支持我们理解记忆的长期目标 一直到单细胞水平，有助于理性发展所必需的知识基础 记忆障碍的新型治疗方法。