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

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...

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Main Authors: Varela, Carmen, Weiss, Sarah A., Meyer, Retsina, Halassa, Michael, Biedenkapp, Joseph, Wilson, Matthew A., Goosens, Ki Ann, Bendor, Daniel
Other Authors: Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Format: Article
Language:en_US
Published: Public Library of Science 2016
Online Access:http://hdl.handle.net/1721.1/103601
https://orcid.org/0000-0002-4155-0346
https://orcid.org/0000-0001-7149-3584
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author Varela, Carmen
Weiss, Sarah A.
Meyer, Retsina
Halassa, Michael
Biedenkapp, Joseph
Wilson, Matthew A.
Goosens, Ki Ann
Bendor, Daniel
author2 Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
author_facet Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Varela, Carmen
Weiss, Sarah A.
Meyer, Retsina
Halassa, Michael
Biedenkapp, Joseph
Wilson, Matthew A.
Goosens, Ki Ann
Bendor, Daniel
author_sort Varela, Carmen
collection MIT
description 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.
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spelling mit-1721.1/1036012022-10-02T06:04:54Z Tracking the Time-Dependent Role of the Hippocampus in Memory Recall Using DREADDs Varela, Carmen Weiss, Sarah A. Meyer, Retsina Halassa, Michael Biedenkapp, Joseph Wilson, Matthew A. Goosens, Ki Ann Bendor, Daniel Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences McGovern Institute for Brain Research at MIT Picower Institute for Learning and Memory Varela, Carmen Weiss, Sarah A. Halassa, Michael Biedenkapp, Joseph Wilson, Matthew A. Goosens, Ki Ann Bendor, Daniel Meyer, Retsina 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) 2016-07-14T16:50:47Z 2016-07-14T16:50:47Z 2016-05 2015-09 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/103601 Varela, Carmen, Sarah Weiss, Retsina Meyer, Michael Halassa, Joseph Biedenkapp, Matthew A. Wilson, Ki Ann Goosens, and Daniel Bendor. "Tracking the Time-Dependent Role of the Hippocampus in Memory Recall Using DREADDs." PLoS ONE 11:5 (2016): e0154374. https://orcid.org/0000-0002-4155-0346 https://orcid.org/0000-0001-7149-3584 en_US http://dx.doi.org/10.1371/journal.pone.0154374 PLOS ONE Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Public Library of Science PLOS
spellingShingle Varela, Carmen
Weiss, Sarah A.
Meyer, Retsina
Halassa, Michael
Biedenkapp, Joseph
Wilson, Matthew A.
Goosens, Ki Ann
Bendor, Daniel
Tracking the Time-Dependent Role of the Hippocampus in Memory Recall Using DREADDs
title Tracking the Time-Dependent Role of the Hippocampus in Memory Recall Using DREADDs
title_full Tracking the Time-Dependent Role of the Hippocampus in Memory Recall Using DREADDs
title_fullStr Tracking the Time-Dependent Role of the Hippocampus in Memory Recall Using DREADDs
title_full_unstemmed Tracking the Time-Dependent Role of the Hippocampus in Memory Recall Using DREADDs
title_short Tracking the Time-Dependent Role of the Hippocampus in Memory Recall Using DREADDs
title_sort tracking the time dependent role of the hippocampus in memory recall using dreadds
url http://hdl.handle.net/1721.1/103601
https://orcid.org/0000-0002-4155-0346
https://orcid.org/0000-0001-7149-3584
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