Abstract
The hippocampus is critical for the storage of new autobiographical experiences as memories. Following an initial encoding stage in the hippocampus, memories undergo a process of systems-level consolidation, which leads to greater stability through time and an increased reliance on neocortical areas for retrieval. The extent to which the retrieval of these consolidated memories still requires the hippocampus is unclear, as both spared and severely degraded remote memory recall have been reported following post-training hippocampal lesions. One difficulty in definitively addressing the role of the hippocampus in remote memory retrieval is the precision with which the entire volume of the hippocampal region can be inactivated. To address this issue, we used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), a chemical-genetic tool capable of highly specific neuronal manipulation over large volumes of brain tissue. We find that remote (>7 weeks after acquisition), but not recent (1–2 days after acquisition) contextual fear memories can be recalled after injection of the DREADD agonist (CNO) in animals expressing the inhibitory DREADD in the entire hippocampus. Our data demonstrate a time-dependent role of the hippocampus in memory retrieval, supporting the standard model of systems consolidation.
Highlights
Hippocampal lesions impair the ability to recall recent episodic experiences, more remote memories are typically spared [1,2,3,4]
We observed no evidence of extinction of the contextual fear memory, as freezing levels were stable over Recent, Remote 1, and Remote 2 Vehicle testing sessions in both control and hM4Di animals (Kruskal-Wallis test, hM4Di: P = 0.37, control: P = 0.11; Fig 3c and 3d)
We have utilized a chemogenetic technique via expression of inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) to reversibly test the time-dependent role of the hippocampus on contextual fear memory retrieval
Summary
Hippocampal lesions impair the ability to recall recent episodic experiences, more remote memories are typically spared [1,2,3,4]. While this would suggest that the hippocampus is not required to retrieve a remote memory, several cases of hippocampal lesions in both humans.
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