Memory strength gates the involvement of a CREB-dependent cortical fear engram in remote memory

Mariana R. Matos, Esther Visser, Ioannis Kramvis, Rolinka J. van der Loo, Titia Gebuis, Robbert Zalm, Priyanka Rao-Ruiz, Huibert D. Mansvelder, August B. Smit, Michel C. van den Oever

Research output: Contribution to JournalArticleAcademicpeer-review


Encoding and retrieval of contextual memories is initially mediated by sparsely activated neurons, so-called engram cells, in the hippocampus. Subsequent memory persistence is thought to depend on network-wide changes involving progressive contribution of cortical regions, a process referred to as systems consolidation. Using a viral-based TRAP (targeted recombination in activated populations) approach, we studied whether consolidation of contextual fear memory by neurons in the medial prefrontal cortex (mPFC) is modulated by memory strength and CREB function. We demonstrate that activity of a small subset of mPFC neurons is sufficient and necessary for remote memory expression, but their involvement depends on the strength of conditioning. Furthermore, selective disruption of CREB function in mPFC engram cells after mild conditioning impairs remote memory expression. Together, our data demonstrate that memory consolidation by mPFC engram cells requires CREB-mediated transcription, with the functionality of this network hub being gated by memory strength.

Original languageEnglish
Article number2315
Pages (from-to)1-11
Number of pages11
JournalNature Communications
Publication statusPublished - 24 May 2019


We thank Yvonne Gouwenberg for AAV packaging and Lizz Fellinger, Lineke Ouwer-kerk, Flora Nelissen and Ioannis Koutlas for assistance with immunohistochemical stainings and imaging. This study was funded by EU MSCA-ITN CognitionNet (FP7-PEOPLE-2013-ITN 607508) to M.R.M., ZonMw VENI grant (916.12.034) to M.C.v.d.O. and VIDI grant (016.168.313) to E.V. and M.C.v.d.O., Amsterdam Neuroscience PoC grant (8-PoC-CIA-2017) to M.C.v.d.O., NWO Veni grant (016.171.033) to P.R-R., and a ZonMw TOP grant (91215030).

FundersFunder number
Amsterdam Neuroscience8-PoC-CIA-2017
ZonMw TOP91215030
Seventh Framework Programme607508
European Commission
Nederlandse Organisatie voor Wetenschappelijk Onderzoek916.12.034, 016.168.313, 016.171.033


    Dive into the research topics of 'Memory strength gates the involvement of a CREB-dependent cortical fear engram in remote memory'. Together they form a unique fingerprint.

    Cite this