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 and Michel C. van den Oever ()
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Mariana R. Matos: Vrije Universiteit Amsterdam
Esther Visser: Vrije Universiteit Amsterdam
Ioannis Kramvis: Vrije Universiteit Amsterdam
Rolinka J. van der Loo: Vrije Universiteit Amsterdam
Titia Gebuis: Vrije Universiteit Amsterdam
Robbert Zalm: Vrije Universiteit Amsterdam
Priyanka Rao-Ruiz: Vrije Universiteit Amsterdam
Huibert D. Mansvelder: Vrije Universiteit Amsterdam
August B. Smit: Vrije Universiteit Amsterdam
Michel C. van den Oever: Vrije Universiteit Amsterdam

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-10266-1

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