TY  - JOUR
AU  - Berdugo-Vega, Gabriel
AU  - Arias-Gil, Gonzalo
AU  - López-Fernández, Adrian
AU  - Artegiani, Benedetta
AU  - Wasielewska, Joanna M
AU  - Lee, Chi-Chieh
AU  - Lippert, Michael T
AU  - Kempermann, Gerd
AU  - Takagaki, Kentaroh
AU  - Calegari, Federico
TI  - Increasing neurogenesis refines hippocampal activity rejuvenating navigational learning strategies and contextual memory throughout life.
JO  - Nature Communications
VL  - 11
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Nature Publishing Group UK
M1  - DZNE-2020-00343
SP  - 135
PY  - 2020
AB  - 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.
KW  - Aging: physiology
KW  - Animals
KW  - Cyclin D1: metabolism
KW  - Cyclin-Dependent Kinase 4: metabolism
KW  - Female
KW  - Hippocampus: physiology
KW  - Learning: physiology
KW  - Memory: physiology
KW  - Memory Consolidation: physiology
KW  - Mice
KW  - Mice, Inbred C57BL
KW  - Neural Stem Cells: physiology
KW  - Neurogenesis: physiology
KW  - Ccnd1 protein, mouse (NLM Chemicals)
KW  - Cyclin D1 (NLM Chemicals)
KW  - Cdk4 protein, mouse (NLM Chemicals)
KW  - Cyclin-Dependent Kinase 4 (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:31919362
C2  - pmc:PMC6952376
DO  - DOI:10.1038/s41467-019-14026-z
UR  - https://pub.dzne.de/record/144979
ER  -