Role of the hippocampus in systems consolidation of remote fear memory

Abstract For decades, the processing and retrieval of memories over weeks or even years have been crucial and fundamental subjects in neuroscience. The hippocampus is essential for episodic memory, including associative fear memory. During remote fear memory formation, the hippocampus serves as an original source of fear memory and distributes memory contents to various brain regions, including the neocortex. Remote memory has a unique feature in terms of the cooperation between distributed regions to restore the original memory trace. Although the hippocampus has traditionally been considered crucial for recent memory processing, several studies have demonstrated that it is also directly involved in remote memory processing. This raises the crucial question: how does the hippocampus transfer the memory trace and at the same time retain recent memory properties? In this Review, we summarize various systems consolidation theories and compare the time-dependent changes in the hippocampus and neocortex. Subsequently, we address the role of the hippocampus and the molecular factors involved in remote memory processing, emphasizing the long-term engagement of the hippocampus. Finally, we aim to investigate memory transfer from the hippocampus to the cortical areas during systems consolidation and examine how this process contributes to fear memory generalization.