Imaging a memory trace over half a life-time in the medial temporal lobe reveals a time-limited role of CA3 neurons in retrieval

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Abstract

Whether retrieval still depends on the hippocampus as memories age or relies then on cortical areas remains a major controversy. Despite evidence for a functional segregation between CA1, CA3 and parahippocampal areas, their specific role within this frame is unclear. Especially, the contribution of CA3 is questionable as very remote memories might be too degraded to be used for pattern completion. To identify the specific role of these areas, we imaged brain activity in mice during retrieval of recent, early remote and very remote fear memories by detecting the immediate-early gene Arc. Investigating correlates of the memory trace over an extended period allowed us to report that, in contrast to CA1, CA3 is no longer recruited in very remote retrieval. Conversely, we showed that parahippocampal areas are then maximally engaged. These results suggest a shift from a greater contribution of the trisynaptic loop to the temporoammonic pathway for retrieval.

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Vanessa Lux

Functional Architecture of Memory unit, Mercator Research Group, Medical Faculty, Ruhr University Bochum, Bochum, Germany

Competing interests
The authors declare that no competing interests exist.
Erika Atucha

Functional Architecture of Memory unit, Mercator Research Group, Medical Faculty, Ruhr University Bochum, Bochum, Germany

Competing interests
The authors declare that no competing interests exist.
Takashi Kitsukawa

Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan

Competing interests
The authors declare that no competing interests exist.
Magdalena M Sauvage

Functional Architecture of Memory unit, Mercator Research Group, Medical Faculty, Ruhr University Bochum, Bochum, Germany

For correspondence
magdalena.sauvage@gmail.com

Competing interests
The authors declare that no competing interests exist.

Ethics

Animal experimentation: All procedures were approved by the Ruhr-Universität Bochum Institutional Animal Use Committee and the LANUV (8.87-51.04.20.09.323)

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.