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

Abstract

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
Volume10
DOIs
Publication statusPublished - 24 May 2019

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