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 学习和记忆是基本的大脑功能，但其潜在的细胞和神经回路 机制仍然很少理解。气味记忆在人类和动物中非常健壮， 生存和繁殖的杰出重要性，并且非常容易受到神经退行性疾病的影响 包括阿尔茨海默氏病。长期以来，嗅觉（梨状）皮质已被建议编码气味记忆， 但是，嗅觉学习的细胞底物和电路机制尚不清楚。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。这个目的 提案是为了对气味记忆的编码方式提供机械细胞/分子的理解，并且 表达。我们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 并操纵在嗅觉学习过程中激活的梨状神经元的活性。目标1：确定 操纵气味记忆痕迹细胞的活性如何改变行为。我们将根据基于遗传标记 CFOS启动子活性（“ fos-tagging”）可视化和操纵梨状神经元的活性 在嗅觉学习过程中激活。目标2：确定嗅觉学习如何改变气味响应 梨状合奏的性质。我们将对醒着的气味诱发活动进行慢性两光子成像， 在厌恶和厌恶嗅觉调节之前，期间和之后行事。我们将测试 假设嗅觉学习有选择地增强了刺激检测和可区分性的编码 构成嗅觉记忆跟踪的神经元。目标3：确定分子身份和连通性 嗅觉记忆痕迹细胞。使用我们先前鉴定的标记基因和单细胞转录组学集 我们将确定在学习过程中激活的梨状神经元的分子身份，我们将追踪 他们的轴突项目。我们提出了一种多层实验方法，以识别 嗅觉学习和记忆，以提供有关神经电路功能如何塑造的机械洞察 经验。 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。我们将开发可靠的软件工具，以进行数据集成，分析， 存储和共享。与软件工程和计算神经科学专家合作，我们 已经构建了用于数据处理的开源标准化代码和文件格式。我们将增强代码鲁棒性 和集成，我们将建立云的兼容性。我们将通过一系列的范围调整管道的使用 开源软件工具并提供图形用户界面。我们提出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共享性，对 一个大型神经科学用户组。