Functional architecture of the cortical network supporting relational memory

支持关系记忆的皮质网络的功能架构

• 批准号: RGPIN-2020-04479
• 负责人: TakeharaNishiuchi, Kaori
• 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: 2020
• 资助国家: 加拿大
• 起止时间: 2020-01-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=717027
• 关键词: Functional; architecture; cortical; network; supporting

We form memory not only to remember the past but also to predict the future. The latter process critically depends on the ability to learn structured relationships among events and make robust inferences that go beyond one's experiences. The long-term goal of my research program is to uncover how the brain forms and stabilizes memories of event relations and later transforms them to infer adaptive behaviour in a new situation. Established literature suggests that relational memories depend on the hippocampus and medial prefrontal cortex (mPFC). These regions are connected through parallel mono- and multi-synaptic pathways. In the next five years, my research team will seek to uncover real-time neural dynamics within these long-range circuits that enable the effective formation and transitive expression of relational memory. To this end, we will conduct parallel studies by combining optogenetics, in vivo electrophysiology, and fiber photometry with well-established relational memory tests in rats. Firstly, we will investigate long-range pathways through which the mPFC controls the effective formation of relational memory in the hippocampus. To date, most studies have focused on the hippocampal-prefrontal interactions during memory consolidation and retrieval. Our recent studies, however, showed that the mPFC network activity tracks the relevance of novel events as they unfold, suggesting that this mPFC's relevancy signal might modulate the encoding of those events in the hippocampus. We propose to identify specific anatomical pathways underlying this novel interaction. Secondly, we will probe neural and circuit mechanisms by which the mPFC transforms relational memories to infer adaptive behaviour in a novel situation. As memories become older, incidental details unique to each memory are mostly forgotten, whereas common latent patterns are retained. This process is presumed to result in the accumulation of generalizable knowledge of the external world, which allows for predicting adaptive behaviour in a novel situation. Recent evidence in humans and rodents suggest that the integration and prediction processes critically depend on the mPFC and its interaction with the hippocampus. We seek to identify neural ensemble activity patterns with which the mPFC network generates prospective signals on a new goal-directed action based on previously learned relational information. In parallel, we will investigate the long-range pathways through which the mPFC interacts with the hippocampus during the transformation of relational memory. These studies will identify the anatomical pathway, timing, and content of the inter-region interactions supporting the effective learning and transitive expression of relational information. Because relational learning and inference are at the core of human intelligence, our study will provide biological insights that speak to fundamental questions about human intellectual abilities and their individual differences.

我们形成记忆不仅是为了记住过去，也是为了预测未来。后一个过程关键取决于学习事件之间的结构化关系并做出超越个人经验的可靠推论的能力。我的研究计划的长期目标是揭示大脑如何形成和稳定事件关系的记忆，然后将它们转化为推断新情况下的适应性行为。现有文献表明，关系记忆依赖于海马体和内侧前额叶皮层（mPFC）。这些区域通过平行的单突触和多突触通路连接。在接下来的五年中，我的研究团队将寻求揭示这些远程回路中的实时神经动力学，从而实现关系记忆的有效形成和传递表达。为此，我们将通过将光遗传学、体内电生理学、纤维光度测量与成熟的大鼠相关记忆测试相结合来进行平行研究。首先，我们将研究 mPFC 控制海马关系记忆有效形成的长程途径。迄今为止，大多数研究都集中在记忆巩固和检索过程中海马-前额叶的相互作用。然而，我们最近的研究表明，mPFC 网络活动会跟踪新事件展开时的相关性，这表明 mPFC 的相关信号可能会调节海马中这些事件的编码。我们建议确定这种新颖相互作用背后的特定解剖途径。其次，我们将探讨 mPFC 转换关系记忆以推断新情况下的适应性行为的神经和回路机制。随着记忆变老，每个记忆特有的附带细节大多会被遗忘，而常见的潜在模式则会被保留。据推测，这个过程会导致外部世界的普遍知识的积累，从而可以预测新情况下的适应性行为。最近在人类和啮齿类动物中的证据表明，整合和预测过程关键取决于 mPFC 及其与海马体的相互作用。我们试图识别神经集合活动模式，mPFC 网络根据先前学习的关系信息生成关于新的目标导向行动的预期信号。与此同时，我们将研究在关系记忆转化过程中 mPFC 与海马体相互作用的长程通路。这些研究将确定区域间相互作用的解剖路径、时间和内容，支持关系信息的有效学习和传递表达。由于关系学习和推理是人类智力的核心，因此我们的研究将提供生物学见解，解答有关人类智力及其个体差异的基本问题。