Imaging and optogenetically manipulating recent and very remote memories reveals that CA1 is required for retrieving gist memories over time and CA3 for memory precision

Episodic memories are hippocampus dependent. Over time such memories undergo consolidation and are thought to transition from precise to gist memories and additionally engage neocortical areas. Whether remote memories still depend on the hippocampus remains a controversy that might stem from the difficulties to distinguish activity from CA1 and CA3 subregions in the hippocampus. CA3 is thought to perform computations that are more time sensitive than CA1 such as pattern completion (completion of a full memory representation based on details). Since details fade over time, we predicted that CA3 would no longer contribute to memory retrieval for very remote memory traces. Further, the contribution of parahippocampal cortical areas which tightly interact with the hippocampus is not well understood. We recently published that indeed CA3 plays a time-limited role in the retrieval of memory while CA1 remains engaged for up to 1-year (equivalent to 40-years-old memory in humans) and that parahippocampal cortical areas were increasingly engaged over time. Here we study the contribution of CA1 and CA3 to the nature (gist/precise) of memory retrieval for recent and up to 1-year-old remote memories using a causal approach. We combined optogenetic cell firing inhibition in CA1 and CA3 with a contextual fear conditioning task to investigate memory precision and measured the neuroanatomical correlates using Arc imaging. While CA3 is required for memory precision at recent time points CA1 contributed to retrieving gist memories independently of the age of the memory trace with the support of the parahippocampal areas for the most remote memories.