RT Journal Article SR Electronic T1 Brain-wide mapping of contextual fear memory engram ensembles supports the dispersed engram complex hypothesis JF bioRxiv FD Cold Spring Harbor Laboratory SP 668483 DO 10.1101/668483 A1 Dheeraj S. Roy A1 Young-Gyun Park A1 Sachie K. Ogawa A1 Jae H. Cho A1 Heejin Choi A1 Lee Kamensky A1 Jared Martin A1 Kwanghun Chung A1 Susumu Tonegawa YR 2019 UL http://biorxiv.org/content/early/2019/06/12/668483.abstract AB SUMMARY Neuronal ensembles that hold specific memory (memory engrams) have been identified in the hippocampus, amygdala, and cortex. It has been hypothesized that engrams for a specific memory are distributed among multiple brain regions that are functionally connected. Here, we report the hitherto most extensive engram map for contextual fear memory by characterizing activity-tagged neurons in 409 regions using SHIELD-based tissue phenotyping. The mapping was aided by a novel engram index, which identified cFos+ brain regions holding engrams with a high probability. Optogenetic manipulations confirmed previously known engrams and revealed new engrams. Many of these engram holding-regions were functionally connected to the CA1 or amygdala engrams. Simultaneous chemogenetic reactivation of multiple engrams, which mimics natural memory recall, conferred a greater level of memory recall than reactivation of a single engram ensemble. Overall, our study supports the hypothesis that a memory is stored in functionally connected engrams distributed across multiple brain regions.