4.8 Article

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

Journal

NATURE COMMUNICATIONS
Volume 12, Issue 1, Pages -

Publisher

NATURE RESEARCH
DOI: 10.1038/s41467-021-21471-2

Keywords

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Funding

  1. NIH [R01 NS104776]
  2. Human Frontiers Science Program [N023241-00_RG105]
  3. NSF Graduate Research Fellowship
  4. Rackham Graduate Fellowship

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Learning-activated engram neurons play a critical role in memory recall but their role in offline memory consolidation is unclear. The authors demonstrate that sleep-associated reactivation of learning-activated sensory neurons is necessary for memory consolidation.
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. Learning-activated engram neurons play a critical role in memory recall but the role of these neurons in offline memory consolidation is unclear. The authors show that sleep-associated reactivation of learning-activated sensory neurons is necessary for memory consolidation.

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