Causal role for sleep-dependent reactivation of learning-activated sensory ensembles for fear memory consolidation

Brittany C. Clawson, Emily J. Pickup, Amy Ensing, Laura Geneseo, James Shaver, John Gonzalez-Amoretti, Meiling Zhao, A. Kane York, Femke Roig Kuhn, Kevin Swift, Jessy D. Martinez, Lijing Wang, Sha Jiang, Sara J. Aton*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Learning-activated engram neurons play a critical role in memory recall. An untested hypothesis is that these same neurons play an instructive role in offline memory consolidation. Here we show that a visually-cued fear memory is consolidated during post-conditioning sleep in mice. We then use TRAP (targeted recombination in active populations) to genetically label or optogenetically manipulate primary visual cortex (V1) neurons responsive to the visual cue. Following fear conditioning, mice respond to activation of this visual engram population in a manner similar to visual presentation of fear cues. Cue-responsive neurons are selectively reactivated in V1 during post-conditioning sleep. Mimicking visual engram reactivation optogenetically leads to increased representation of the visual cue in V1. Optogenetic inhibition of the engram population during post-conditioning sleep disrupts consolidation of fear memory. We conclude that selective sleep-associated reactivation of learning-activated sensory populations serves as a necessary instructive mechanism for memory consolidation.

Original languageEnglish
Article number1200
Pages (from-to)1-13
Number of pages13
JournalNature Communications
Issue number1
Early online date22 Feb 2021
Publication statusPublished - Dec 2021

Bibliographical note

Funding Information:
The authors are grateful to members of the Aton laboratory and to Dr. Natalie Tronson, Dr. Monica Dus, Dr. Richard Hume, and Dr. Dawen Cai for helpful feedback on this manuscript. This work was supported by research grants from the NIH (R01 NS104776) and the Human Frontiers Science Program (N023241-00_RG105) to S.J.A., a NSF Graduate Research Fellowship to B.C.C., and a Rackham Graduate Fellowship to B.C.C.

Publisher Copyright:
© 2021, The Author(s).

Copyright 2021 Elsevier B.V., All rights reserved.


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