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Neurogenesis-mediated forgetting of complex paired-associates memories

Jonathan R Epp, Leigh C.P. Botly, Sheena A Josselyn, Paul W Frankland
doi: https://doi.org/10.1101/2021.03.25.437009
Jonathan R Epp
1Hotchkiss Brain Institute, University of Calgary, Calgary Alberta Canada, T2N 4N1
2Department of Cell Biology, University of Calgary, Calgary Alberta Canada, T2N 4N1
3Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Canada, M5G 1X8
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  • For correspondence: jonathan.epp1@ucalgary.ca paul.frankland@sickkids.ca
Leigh C.P. Botly
1Hotchkiss Brain Institute, University of Calgary, Calgary Alberta Canada, T2N 4N1
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Sheena A Josselyn
3Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Canada, M5G 1X8
4Department of Psychology, University of Toronto, Toronto, Canada, Ontario, M5S 3GM
5Department of Physiology, University of Toronto, Toronto, Canada, Ontario, M5S 1A8
6Institute of Medical Science, University of Toronto, Toronto, Canada, Ontario, M5S 1A8
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Paul W Frankland
3Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Canada, M5G 1X8
4Department of Psychology, University of Toronto, Toronto, Canada, Ontario, M5S 3GM
5Department of Physiology, University of Toronto, Toronto, Canada, Ontario, M5S 1A8
6Institute of Medical Science, University of Toronto, Toronto, Canada, Ontario, M5S 1A8
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  • For correspondence: jonathan.epp1@ucalgary.ca paul.frankland@sickkids.ca
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Abstract

The hippocampus is a critical structure involved in many forms of learning and memory. It is also one of the only regions in the adult mammalian brain that continues to generate new neurons throughout adulthood. This process of adult neurogenesis may increase the plasticity of the hippocampus which could be beneficial for learning but has also been demonstrated to decrease the stability of previously acquired memories. Here we test whether increased production of new neurons following the formation of a gradually acquired paired-associates task will result in forgetting of this type of memory. We trained mice in a touchscreen-based object/location task and then increased neurogenesis using voluntary exercise. Our results indicate that mice with increased neurogenesis show poor recall of the previously established memory. When subsequently exposed to a reversal task we also show that mice with increased neurogenesis require fewer correction trials to acquire the new task contingencies. This suggests that prior forgetting reduces perseveration on the now outdated memory. Together our results add to a growing body of literature which indicates the important role of adult neurogenesis in destabilizing previously acquired memories to allow for flexible encoding of new memories.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted March 25, 2021.
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Neurogenesis-mediated forgetting of complex paired-associates memories
Jonathan R Epp, Leigh C.P. Botly, Sheena A Josselyn, Paul W Frankland
bioRxiv 2021.03.25.437009; doi: https://doi.org/10.1101/2021.03.25.437009
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Neurogenesis-mediated forgetting of complex paired-associates memories
Jonathan R Epp, Leigh C.P. Botly, Sheena A Josselyn, Paul W Frankland
bioRxiv 2021.03.25.437009; doi: https://doi.org/10.1101/2021.03.25.437009

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