Allen, T. A. | bioRxiv Science

bioRxiv2018

Prefrontal pathways provide top down control of memory for sequences of events

We remember our lives as sequences of events, but it is unclear how these memories are controlled during retrieval. In rats, prelimbic cortex (PL) is positioned to influence sequence memory through extensive top down inputs to the nucleus reuniens of the thalamus (RE) and perirhinal cortex (PER), regions heavily interconnected with the hippocampus. Here, we tested the hypothesis that specific PLRE and PLPER projections regulate sequence memory retrieval using an hM4Di synaptic-silencing approach. First, we show that the suppression of PL activity impairs sequence memory. Second, we show that inhibiting PLRE and PLPER pathways effectively eliminated sequence memory. Last, we performed a sequential lag analysis showing that the PLRE pathway contributes to a working memory retrieval strategy, and the PLPER pathway contributes to a temporal context memory retrieval strategy. These results demonstrate that the PLRE and PLPER pathways serve as top down mechanisms that control sequence memory retrieval strategies.

neuroscience↗

bioRxiv2018

Hippocampus activations reflect temporal contexts while medial prefrontal cortex activations reflect ordinal positions during sequence memory in humans

Remembering sequences of events defines episodic memory, but retrieval can be driven by both ordinality and temporal contexts. Whether these modes of retrieval operate at the same time or not remains unclear. Theoretically, medial prefrontal cortex (mPFC) confers ordinality, while the hippocampus (HC) associates events in gradually changing temporal contexts. Here, we looked for evidence of each with BOLD fMRI in a sequence task that taxes both retrieval modes. To test ordinal modes, items were transferred between sequences but retained their position (e.g., AB3). Ordinal modes activated mPFC, but not HC. To test temporal contexts, we examined items that skipped ahead across lag distances (e.g., ABD). HC, but not mPFC, tracked temporal contexts. There was a mPFC and HC by retrieval mode interaction. These current results suggest that the mPFC and HC are concurrently engaged in different retrieval modes in support of remembering when an event occurred. Significance StatementMemory for sequences of events is a defining aspect of everyday episodic memory allowing our brain to separate unique experiences that otherwise have overlapping sensory and spatial content. Sequence memory is impaired in typical aging and in disorders such as Alzheimers disease. The results of the current study provide new evidence that two retrieval modes concurrently arise during sequence memory, and they have distinct neural correlates. The medial prefrontal cortex contributes to an ordinal retrieval mode, while at the same time, the hippocampus contributes a gradually-changing temporal context mode of retrieval. These data shed new light on why typical episodic memory requires both the medial prefrontal cortex and the hippocampus, and suggests a functional dissociation between the medial prefrontal cortex and hippocampus across these modes of retrieval.

neuroscience↗