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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=764270
• 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结构化关系的能力，并做出超越个人经验的强有力的推论。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行为。已有的文献表明，关系记忆依赖于海马和内侧前额叶皮层（mPFC）。这些区域通过平行的单突触和多突触通路连接。在接下来的五年里，我的研究团队将寻求揭示这些长程回路中的实时神经动力学，这些回路使关系记忆的有效形成和传递表达成为可能。为此，我们将通过结合光遗传学、体内电生理学和纤维光度学与大鼠中成熟的关系记忆测试来进行平行研究。首先，我们将研究mPFC控制海马中关系记忆有效形成的长程通路。迄今为止，大多数研究集中在记忆巩固和提取过程中的前额叶-大脑半球的相互作用。然而，我们最近的研究表明，mPFC网络活动在新事件展开时跟踪它们的相关性，这表明mPFC的相关信号可能会调节海马体中这些事件的编码。我们建议识别这种新型相互作用背后的特定解剖路径。其次，我们将探讨神经和电路的机制，mPFC转换关系记忆推断适应性行为在一个新的情况下。随着记忆的老化，每个记忆中独特的偶然细节大多被遗忘，而共同的潜在模式则被保留下来。这个过程被认为是导致外部世界的可推广知识的积累，这使得预测适应行为在一个新的情况。最近在人类和啮齿动物中的证据表明，整合和预测过程严重依赖于mPFC及其与海马的相互作用。我们试图识别神经集成活动模式，mPFC网络根据先前学习的关系信息在新的目标导向行动上产生预期信号。与此同时，我们将调查的长距离途径，通过该mPFC与海马相互作用的关系记忆的转换过程中。这些研究将确定区域间相互作用的解剖学途径，时间和内容，支持有效的学习和关系信息的传递表达。由于关系学习和推理是人类智力的核心，我们的研究将提供生物学见解，这些见解涉及人类智力能力及其个体差异的基本问题。