Tracking the Time-Dependent Role of the Hippocampus in Memory Recall Using DREADDs

• Main Authors: Varela, Carmen (Contributor), Weiss, Sarah A. (Contributor), Meyer, Retsina (Contributor), Halassa, Michael (Contributor), Biedenkapp, Joseph (Contributor), Wilson, Matthew A. (Contributor), Goosens, Ki Ann (Contributor), Bendor, Daniel (Contributor)
• Other Authors: Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences (Contributor), McGovern Institute for Brain Research at MIT (Contributor), Picower Institute for Learning and Memory (Contributor)
• Format: Article
• Language: English
• Published: Public Library of Science, 2016-07-14T16:50:47Z.
• Subjects: Article
• Online Access: Get fulltext

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.
National Institute of Mental Health (U.S.) (NIMH (5R01MH061976))
National Institute of Mental Health (U.S.) (NIMH (R01 MH084966))
United States. Defense Advanced Research Projects Agency (Grant W911NF-10-1-0059)
European Research Council (ERC) (Horizon 2020: ERC starter grant-CHIME)