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Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life

Functional plasticity of the brain decreases during ageing causing marked deficits in contextual learning, allocentric navigation and episodic memory. Adult neurogenesis is a prime example of hippocampal plasticity promoting the contextualisation of information and dramatically decreases during agei...

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Autores principales: Berdugo-Vega, Gabriel, Arias-Gil, Gonzalo, López-Fernández, Adrian, Artegiani, Benedetta, Wasielewska, Joanna M., Lee, Chi-Chieh, Lippert, Michael T., Kempermann, Gerd, Takagaki, Kentaroh, Calegari, Federico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952376/
https://www.ncbi.nlm.nih.gov/pubmed/31919362
http://dx.doi.org/10.1038/s41467-019-14026-z
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author Berdugo-Vega, Gabriel
Arias-Gil, Gonzalo
López-Fernández, Adrian
Artegiani, Benedetta
Wasielewska, Joanna M.
Lee, Chi-Chieh
Lippert, Michael T.
Kempermann, Gerd
Takagaki, Kentaroh
Calegari, Federico
author_facet Berdugo-Vega, Gabriel
Arias-Gil, Gonzalo
López-Fernández, Adrian
Artegiani, Benedetta
Wasielewska, Joanna M.
Lee, Chi-Chieh
Lippert, Michael T.
Kempermann, Gerd
Takagaki, Kentaroh
Calegari, Federico
author_sort Berdugo-Vega, Gabriel
collection PubMed
description Functional plasticity of the brain decreases during ageing causing marked deficits in contextual learning, allocentric navigation and episodic memory. Adult neurogenesis is a prime example of hippocampal plasticity promoting the contextualisation of information and dramatically decreases during ageing. We found that a genetically-driven expansion of neural stem cells by overexpression of the cell cycle regulators Cdk4/cyclinD1 compensated the age-related decline in neurogenesis. This triggered an overall inhibitory effect on the trisynaptic hippocampal circuit resulting in a changed profile of CA1 sharp-wave ripples known to underlie memory consolidation. Most importantly, increased neurogenesis rescued the age-related switch from hippocampal to striatal learning strategies by rescuing allocentric navigation and contextual memory. Our study demonstrates that critical aspects of hippocampal function can be reversed in old age, or compensated throughout life, by exploiting the brain’s endogenous reserve of neural stem cells.
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spelling pubmed-69523762020-01-13 Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life Berdugo-Vega, Gabriel Arias-Gil, Gonzalo López-Fernández, Adrian Artegiani, Benedetta Wasielewska, Joanna M. Lee, Chi-Chieh Lippert, Michael T. Kempermann, Gerd Takagaki, Kentaroh Calegari, Federico Nat Commun Article Functional plasticity of the brain decreases during ageing causing marked deficits in contextual learning, allocentric navigation and episodic memory. Adult neurogenesis is a prime example of hippocampal plasticity promoting the contextualisation of information and dramatically decreases during ageing. We found that a genetically-driven expansion of neural stem cells by overexpression of the cell cycle regulators Cdk4/cyclinD1 compensated the age-related decline in neurogenesis. This triggered an overall inhibitory effect on the trisynaptic hippocampal circuit resulting in a changed profile of CA1 sharp-wave ripples known to underlie memory consolidation. Most importantly, increased neurogenesis rescued the age-related switch from hippocampal to striatal learning strategies by rescuing allocentric navigation and contextual memory. Our study demonstrates that critical aspects of hippocampal function can be reversed in old age, or compensated throughout life, by exploiting the brain’s endogenous reserve of neural stem cells. Nature Publishing Group UK 2020-01-09 /pmc/articles/PMC6952376/ /pubmed/31919362 http://dx.doi.org/10.1038/s41467-019-14026-z Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Berdugo-Vega, Gabriel
Arias-Gil, Gonzalo
López-Fernández, Adrian
Artegiani, Benedetta
Wasielewska, Joanna M.
Lee, Chi-Chieh
Lippert, Michael T.
Kempermann, Gerd
Takagaki, Kentaroh
Calegari, Federico
Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life
title Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life
title_full Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life
title_fullStr Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life
title_full_unstemmed Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life
title_short Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life
title_sort increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952376/
https://www.ncbi.nlm.nih.gov/pubmed/31919362
http://dx.doi.org/10.1038/s41467-019-14026-z
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