Deconstructing neural circuits underlying olfactory episodic memory

解构嗅觉情景记忆的神经回路

• 批准号: RGPIN-2019-06448
• 负责人: kim, junchul
• 金额: $ 4.01万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=738916
• 关键词: Deconstructing; neural; circuits; underlying; olfactory

Concept: Where and when did I smell that apple pie before? Ability to detect chemical signals in the environment and remember elements of a unique olfactory event is essential for making sense of the present, forming predictions about the future, and the selection of behaviours for survival and reproduction. For example, animals use olfaction and olfactory memory to locate predators, foods, social hierarchy, mating partners, and caregivers. Decades of research have revealed how specific odours are detected and processed by the olfactory system to perceive odours. However, it remains unknown how our brain forms a memory of detailed contextual information about unique olfactory events. To address this knowledge gap, we have pioneered a model system for olfactory episodic memory, constituted by a hard-wired connectivity between the hippocampus and the olfactory cortex, and a robust behavioural readout of contextual elements of olfactory memory. In the present proposal, we use this system to study a neural mechanism underlying olfactory episodic memory. Objectives: To understand how olfactory memory is formed and expressed in brain at circuit level, we use a combination of anatomical tracing, activity-dependent cell labeling, and live brain imaging and manipulation. By combining the preliminary findings of the above approaches, we have recently discovered that neural signals from hippocampus are spatially organized within the olfactory cortex to carry distinct spatial and temporal context of olfactory memory. As a five year NSERC proposal, we will focus on understanding how olfactory events are represented by specific cells within the olfactory cortex and demonstrate that their activity can be manipulated to alter the memory. Next, we will expand our findings to investigate how the activity of olfactory cortex evolves over time to faithfully recapitulate olfactory memory. Our specific short-term objectives are: Study 1. We will identify the olfactory memory trace that is represented by the anterior olfactory nucleus (AON) using the TRAP approach. Study 2. We will determine a causal contribution of the AON in olfactory memory using optogenetic manipulation. Study 3. We will demonstrate how a unique olfactory memory trace is formed and stabilized within the AON, and later reactivated during memory recall in a hippocampus-dependent manner using calcium imaging. Significance: Numerous human brain imaging studies have shown that olfactory areas are reactivated during recollection of olfactory episodes. However, the underlying neural mechanism remains unknown. The proposed research program will demonstrate for the first time that the AON is the storehouse of olfactory episodic memory, and provide a novel insight into the universal mechanism of episodic odour memory formation and recall. Given its novelty and the expected conceptual advance, we expect the proposed research to be of great interest to many fields in the natural sciences and engineering.

概念：我之前在哪里、什么时候闻到过苹果派的味道？检测环境中的化学信号并记住独特嗅觉事件元素的能力对于理解现在、形成对未来的预测以及选择生存和繁殖行为至关重要。例如，动物利用嗅觉和嗅觉记忆来定位捕食者、食物、社会等级、交配伙伴和照顾者。数十年的研究揭示了嗅觉系统如何检测和处理特定气味以感知气味。然而，我们的大脑如何形成有关独特嗅觉事件的详细上下文信息的记忆仍然未知。为了解决这一知识差距，我们开创了嗅觉情景记忆的模型系统，该系统由海马体和嗅觉皮层之间的硬连线连接以及嗅觉记忆的上下文元素的强大行为读出构成。在本提案中，我们使用该系统来研究嗅觉情景记忆背后的神经机制。目标：为了了解嗅觉记忆是如何在大脑回路水平形成和表达的，我们结合使用解剖追踪、活动依赖性细胞标记以及活体大脑成像和操作。通过结合上述方法的初步发现，我们最近发现来自海马体的神经信号在嗅觉皮层内进行空间组织，以携带嗅觉记忆的不同空间和时间背景。作为 NSERC 的一项为期五年的提案，我们将重点了解嗅觉皮层内的特定细胞如何代表嗅觉事件，并证明可以操纵它们的活动来改变记忆。接下来，我们将扩展我们的发现，研究嗅觉皮层的活动如何随着时间的推移而演变，以忠实地再现嗅觉记忆。 我们具体的短期目标是： 研究 1。我们将使用 TRAP 方法识别由前嗅核 (AON) 代表的嗅觉记忆痕迹。研究 2. 我们将使用光遗传学操作来确定 AON 在嗅觉记忆中的因果贡献。研究 3. 我们将展示独特的嗅觉记忆痕迹如何在 AON 内形成和稳定，然后使用钙成像以海马依赖性方式在记忆回忆过程中重新激活。意义：大量人类大脑成像研究表明，在回忆嗅觉事件时，嗅觉区域会被重新激活。然而，潜在的神经机制仍然未知。拟议的研究计划将首次证明 AON 是嗅觉情景记忆的仓库，并为情景气味记忆形成和回忆的普遍机制提供新的见解。鉴于其新颖性和预期的概念进步，我们预计所提出的研究将引起自然科学和工程学的许多领域的极大兴趣。