The organization of recent and remote memories

Key Points In humans, damage to the medial temporal lobe typically produces temporally-graded retrograde amnesia — a loss of recent memories, but a relative sparing of more remote ones. This has been taken as evidence that the hippocampus has a time-limited role in the storage and retrieval of some forms of memory. This idea forms the central tenet of most contemporary views of system consolidation: the hippocampus acts as a temporary store for new information, but permanent storage depends on a broadly distributed cortical network. The relationship between hippocampal damage and retrograde amnesia has been studied in animal models. The main advantage of this approach is that it allows retrograde amnesia to be studied in a prospective manner — the extent of the lesion can be controlled, as can what is learned and when. As in humans, the typical finding is that disrupting hippocampal function preferentially affects recent, rather than remote, memories. These observations in humans and animal models indicate that memories are reorganized at the system level as they mature. Most contemporary models propose that experience is initially encoded in parallel in hippocampal and cortical networks. Subsequent reactivation of the hippocampal network reinstates activity in different cortical networks. This coordinated replay across hippocampal–cortical networks leads to gradual strengthening of cortico-cortical connections, which eventually allows new memories to become independent of the hippocampus and to be gradually integrated with pre-existing cortical memories. By contrast, multiple trace theory proposes a more permanent role for the hippocampus in some forms of declarative memory. It posits that memories are encoded in hippocampal–cortical networks, and that retrieval of contextually rich episodic memories, as well as spatial detail, always requires the hippocampus. Memory reactivation is the core mechanism in consolidation models. Reactivation of the hippocampal memory trace is thought to lead to the reinstatement of waking patterns of neural activity in the cortex, and subsequent stabilization and refinement of hippocampal–cortical circuits. Gradual remodelling of hippocampal–cortical circuits depends on several rounds of synaptic modification. These changes are initiated in a reactivation-dependent manner, either during online (task-relevant) or offline (sleep or quiet wakefulness) situations, and require the expression of new genes. Imaging studies in roden