Odor Memory Traces in the Mouse Olfactory Cortex - Supplement

小鼠嗅觉皮层中的气味记忆痕迹 - 补充

• 批准号: 10405361
• 负责人: Alexander Fleischmann
• 金额: $ 23.93万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10405361
• 关键词: Alzheimer' s Disease; Animals; Axon; Behavior; Behavior monitoring; Behavioral; Brain; Calcium; Cells; Chronic; Code; Collaborations; Communities; Complement; Computer software; Custom; Data; Data Set; Data Sources; Desire for food; Detection; Ecosystem; Electrophysiology (science); Feedback; Fluorescence; Foundations; Free Will; Future; Generations; Genes; Genetic; Goals; Human; Image; Imaging Device; Learning; Linux; Manuals; Memory; Metadata; Modernization; Molecular; Molecular Genetics; Mus; Neurodegenerative Disorders; Neurons; Neurosciences; Odors; Olfactory Cortex; Olfactory Learning; Output; Process; Property; Pythons; Reproducibility; Reproduction; Research Personnel; Smell Perception; Software Engineering; Software Tools; Standardization; Stimulus; System; Testing; Vendor; Work; application programming interface; awake; base; computational neuroscience; computerized data processing; conditioning; data format; data integration; data management; experience; experimental study; file format; fluorescence imaging; genetic approach; graphical user interface; improved; in vivo calcium imaging; in vivo imaging; innovation; insight; memory encoding; multimodal data; neural circuit; open source; open source tool; optogenetics; parent grant; piriform cortex; promoter; relating to nervous system; repository; response; sensor; service providers; sound; tool; transcriptomics; two-photon; usability

Project Summary Learning and memory are fundamental brain functions, yet their underlying cellular and neural circuit mechanisms remain poorly understood. Odor memories are exceptionally robust in humans and animals, of outstanding importance for survival and reproduction, and highly susceptible to neurodegenerative disorders including Alzheimer Disease. The olfactory (piriform) cortex has long been suggested to encode odor memories, however, the cellular substrates and circuit mechanisms of olfactory learning are unknown. Our long-term goal is to understand the cellular and neural circuit mechanisms of odor perception and memory. The objective of this proposal is to provide a mechanistic cellular/molecular understanding of how odor memories are encoded and expressed. We have developed activity-based intersectional genetic approaches in mice that allow us to identify and manipulate the activity of piriform neurons that were activated during olfactory learning. Aim 1: To determine how manipulating the activity of odor memory trace cells alters behavior. We will use genetic tagging based on cFos promoter activity (“Fos-tagging”) to visualize and manipulate the activity of piriform neurons that were activated during olfactory learning. Aim 2: To determine how olfactory learning alters the odor response properties of piriform ensembles. We will perform chronic two-photon imaging of odor-evoked activity in awake, behaving mice, before, during, and after aversive and appetitive olfactory conditioning. We will test the hypothesis that olfactory learning selectively enhances the encoding of stimulus detection and discriminability in neurons constituting an olfactory memory trace. Aim 3: To determine the molecular identity and connectivity of olfactory memory trace cells. Using our previously identified set of marker genes and single cell transcriptomics we will determine the molecular identities of piriform neurons that are activated during learning, and we will trace their axonal projections. We propose a multi-tiered experimental approach to identify the cellular substrates for olfactory learning and memory, to provide mechanistic insight into how neural circuit functions are shaped by experience. Achieving our goals requires the generation and analysis of large, multimodal data sets, including chronic in vivo calcium imaging and behavioral monitoring. We will develop robust software tools for data integration, analysis, storage, and sharing. In collaboration with experts in software engineering and computational neuroscience we have built open-source standardized code and file formats for data processing. We will enhance code robustness and integration, and we will establish cloud compatibility. We will adapt our pipeline for usage with a range of open-source software tools and provide a graphical user interface. The innovative software solutions we propose will enhance reproducibility and shareability of integrated neural activity and behavioral data, with significance to a large neuroscience user group.

项目摘要 学习和记忆是大脑的基本功能，但它们的细胞和神经回路 机制仍然知之甚少。气味记忆在人类和动物中非常强大， 对生存和繁殖具有突出的重要性，并且非常容易患神经退行性疾病 包括老年痴呆症长期以来，人们一直认为嗅觉（梨状）皮层对气味记忆进行编码， 然而，嗅觉学习的细胞基质和回路机制尚不清楚。我们的长期目标 是了解气味感知和记忆的细胞和神经回路机制。的目的 一个建议是提供一个机械的细胞/分子的理解如何气味记忆编码， 表达。我们已经在小鼠中开发了基于活动的交叉遗传方法，使我们能够识别 并控制在嗅觉学习过程中被激活的梨状神经元的活动。目标1：确定 如何操纵气味记忆跟踪细胞的活动改变行为。我们将使用基因标记， cFos启动子活性（“Fos-标记”），以可视化和操纵梨状神经元的活性， 在嗅觉学习期间激活。目的2：确定嗅觉学习如何改变气味反应 梨状神经丛的性质。我们将对清醒时的气味诱发活动进行慢性双光子成像， 行为小鼠，之前，期间和之后厌恶和食欲嗅觉条件反射。我们将测试 假设嗅觉学习选择性地增强刺激检测和辨别的编码， 构成嗅觉记忆痕迹的神经元。目的3：确定分子身份和连接性 嗅觉记忆追踪细胞利用我们先前鉴定的一组标记基因和单细胞转录组学 我们将确定在学习过程中激活的梨状神经元的分子身份， 它们的轴突投射我们提出了一种多层次的实验方法来确定细胞基质， 嗅觉学习和记忆，以提供机制洞察神经回路功能是如何形成的， 体验. 实现我们的目标需要生成和分析大型多模式数据集，包括慢性体内 钙成像和行为监测。我们将开发强大的软件工具，用于数据集成，分析， 存储和共享。在与软件工程和计算神经科学专家的合作中， 已经建立了用于数据处理的开源标准化代码和文件格式。我们将增强代码的健壮性 和集成，我们将建立云兼容性。我们将调整我们的管道，以适应一系列 开源软件工具，并提供图形用户界面。我们提供的创新软件解决方案 将提高综合神经活动和行为数据的可重复性和可共享性， 一个庞大的神经科学用户群。