Prefrontal Pathways Provide Top-Down Control of Memory for Sequences of Events

• Main Authors: Maanasa Jayachandran, Stephanie B. Linley, Maximilian Schlecht, Stephen V. Mahler, Robert P. Vertes, Timothy A. Allen
• Format: Article
• Language: English
• Published: Elsevier 2019-07-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124719308265

Summary: We remember our lives as sequences of events, but it is unclear how these memories are controlled during retrieval. In rats, the medial prefrontal cortex (mPFC) is positioned to influence sequence memory through extensive top-down inputs to regions heavily interconnected with the hippocampus, notably the nucleus reuniens of the thalamus (RE) and perirhinal cortex (PER). Here, we used an hM4Di synaptic-silencing approach to test our hypothesis that specific mPFC→RE and mPFC→PER projections regulate sequence memory retrieval. First, we found non-overlapping populations of mPFC cells project to RE and PER. Second, suppressing mPFC activity impaired sequence memory. Third, inhibiting mPFC→RE and mPFC→PER pathways effectively abolished sequence memory. Finally, a sequential lag analysis showed that the mPFC→RE pathway contributes to a working memory retrieval strategy, whereas the mPFC→PER pathway supports a temporal context memory retrieval strategy. These findings demonstrate that mPFC→RE and mPFC→PER pathways serve as top-down mechanisms that control distinct sequence memory retrieval strategies. : Jayachandran et al. demonstrate that the medial prefrontal cortex has separate projections to the nucleus reuniens of the thalamus and perirhinal cortex. The authors then demonstrate that these pathways differentially control how an episodic-like memory is retrieved. Keywords: thalamus, nucleus reuniens, perirhinal cortex, DREADDs, episodic memory, memory retrieval, working memory, temporal context, cognitive control, hippocampus