Functional architecture of the cortical network supporting relational memory

点击翻译按钮获取中文摘要

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.