Abstract
Neuronal ensembles that hold specific memory (memory engrams) have been identified in the hippocampus, amygdala, or cortex. However, it has been hypothesized that engrams of a specific memory are distributed among multiple brain regions that are functionally connected, referred to as a unified engram complex. Here, we report a partial map of the engram complex for contextual fear conditioning memory by characterizing encoding activated neuronal ensembles in 247 regions using tissue phenotyping in mice. The mapping was aided by an engram index, which identified 117 cFos+ brain regions holding engrams with high probability, and brain-wide reactivation of these neuronal ensembles by recall. Optogenetic manipulation experiments revealed engram ensembles, many of which were functionally connected to hippocampal or amygdala engrams. Simultaneous chemogenetic reactivation of multiple engram ensembles conferred a greater level of memory recall than reactivation of a single engram ensemble, reflecting the natural memory recall process. Overall, our study supports the unified engram complex hypothesis for memory storage.
| Original language | English |
|---|---|
| Article number | 1799 |
| Journal | Nature communications |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 2022 Dec |
Bibliographical note
Funding Information:We thank S. Huang, L. Smith, F. Bushard, A. Hamalian, D. King, C. Ragion, W. Yu, C. Lovett, and Y. Hou for help with experiments; C. Sun, S. Muralidhar, and Q. Ferry for comments; A. Schroeder for proofreading; and all members of the Chung and Tonegawa laboratories for their support. This work was supported by the Warren Alpert Distinguished Scholar Award and NIH 1K99NS125121-01 (to D.R.), by the Burroughs Wellcome Fund Career Award at the Scientific Interface, Searle Scholars Program, Packard Award in Science and Engineering, NARSAD Young Investigator Award, McKnight Foundation Technology Award, JPB Foundation (PIIF and PNDRF), NCSOFT Cultural Foundation, the Institute for Basic Science IBS-R026-D1, and NIH (1-DP2-ES027992) (to K.C.), and by the RIKEN Center for Brain Science, Howard Hughes Medical Institute, and JPB Foundation (to S.T.).
Funding Information:
We thank S. Huang, L. Smith, F. Bushard, A. Hamalian, D. King, C. Ragion, W. Yu, C. Lovett, and Y. Hou for help with experiments; C. Sun, S. Muralidhar, and Q. Ferry for comments; A. Schroeder for proofreading; and all members of the Chung and Tonegawa laboratories for their support. This work was supported by the Warren Alpert Distinguished Scholar Award and NIH 1K99NS125121-01 (to D.R.), by the Burroughs Wellcome Fund Career Award at the Scientific Interface, Searle Scholars Program, Packard Award in Science and Engineering, NARSAD Young Investigator Award, McKnight Foundation Technology Award, JPB Foundation (PIIF and PNDRF), NCSOFT Cultural Foundation, the Institute for Basic Science IBS-R026-D1, and NIH (1-DP2-ES027992) (to K.C.), and by the RIKEN Center for Brain Science, Howard Hughes Medical Institute, and JPB Foundation (to S.T.).
Publisher Copyright:
© 2022, The Author(s).
All Science Journal Classification (ASJC) codes
- General
- Physics and Astronomy(all)
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)