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bioRxiv · 10.1101/668483

Brain-wide mapping of contextual fear memory engram ensembles supports the dispersed engram complex hypothesis

Roy, D. S.·Park, Y.-G.·Ogawa, S. K.·Cho, J. H.·Choi, H.·Kamensky, L.·Martin, J.·Chung, K.·Tonegawa, S.
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Abstract

GRAPHICAL ABSTRACT\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=145 SRC=\"FIGDIR/small/668483v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (34K):\norg.highwire.dtl.DTLVardef@1957e90org.highwire.dtl.DTLVardef@1a83d79org.highwire.dtl.DTLVardef@5bd5d5org.highwire.dtl.DTLVardef@133c879_HPS_FORMAT_FIGEXP M_FIG C_FIG SUMMARYNeuronal 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.

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Roy, D. S., Park, Y.-G., Ogawa, S. K., Cho, J. H., Choi, H., Kamensky, L., Martin, J., Chung, K., Tonegawa, S.. 2019-06-12. Brain-wide mapping of contextual fear memory engram ensembles supports the dispersed engram complex hypothesis. https://doi.org/10.1101/668483

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