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.
Bibliographical noteFunding 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.
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