Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats

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Titel: Dentate gyrus-specific knockdown of adult neurogenesis impairs spatial and object recognition memory in adult rats
Autoren: Jessberger S, Clark RE, Broadbent NJ, Clemenson GD Jr, CONSIGLIO, Antonella, Lie DC, Squire LR, Gage F.H.
Weitere Verfasser: Universitat de Barcelona
Quelle: LEARN MEMORY
r-FSJD: Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
Fundació Sant Joan de Déu
Recercat. Dipósit de la Recerca de Catalunya
instname
r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
Articles publicats en revistes (Patologia i Terapèutica Experimental)
Dipòsit Digital de la UB
Universidad de Barcelona
Verlagsinformationen: Cold Spring Harbor Laboratory, 2009.
Publikationsjahr: 2009
Schlagwörter: Male, 0301 basic medicine, Space perception, Hipocamp (Cervell), Percepció de l'espai, Genetic Vectors, Rats as laboratory animals, Neurones, Social Environment, Animals, Genetically Modified, Rats, Sprague-Dawley, Stereotaxic Techniques, Food Preferences, 03 medical and health sciences, Limbic system, 0302 clinical medicine, Memory, Animals, Maze Learning, Rates (Animals de laboratori), Neurons, Percepció de les formes, Lentivirus, Recognition, Psychology, Form perception, Rats, 3. Good health, Form Perception, Wnt Proteins, Sistema límbic, Space Perception, Dentate Gyrus, Hippocampus (Brain), Psychomotor Performance, Memòria
Beschreibung: New granule cells are born throughout life in the dentate gyrus of the hippocampal formation. Given the fundamental role of the hippocampus in processes underlying certain forms of learning and memory, it has been speculated that newborn granule cells contribute to cognition. However, previous strategies aiming to causally link newborn neurons with hippocampal function used ablation strategies that were not exclusive to the hippocampus or that were associated with substantial side effects, such as inflammation. We here used a lentiviral approach to specifically block neurogenesis in the dentate gyrus of adult male rats by inhibiting WNT signaling, which is critically involved in the generation of newborn neurons, using a dominant-negative WNT (dnWNT). We found a level-dependent effect of adult neurogenesis on the long-term retention of spatial memory in the water maze task, as rats with substantially reduced levels of newborn neurons showed less preference for the target zone in probe trials >2 wk after acquisition compared with control rats. Furthermore, animals with strongly reduced levels of neurogenesis were impaired in a hippocampus-dependent object recognition task. Social transmission of food preference, a behavioral test that also depends on hippocampal function, was not affected by knockdown of neurogenesis. Here we identified a role for newborn neurons in distinct aspects of hippocampal function that will set the ground to further elucidate, using experimental and computational strategies, the mechanism by which newborn neurons contribute to behavior.
Publikationsart: Article
Dateibeschreibung: application/pdf
Sprache: English
ISSN: 1549-5485
1072-0502
DOI: 10.1101/lm.1172609
Zugangs-URL: http://learnmem.cshlp.org/content/16/2/147.full.pdf
https://pubmed.ncbi.nlm.nih.gov/19181621
http://fundanet.fsjd.org/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=12114
http://hdl.handle.net/2445/107102
https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=12114
https://hdl.handle.net/2445/107102
http://diposit.ub.edu/dspace/handle/2445/107102
https://www.ncbi.nlm.nih.gov/pubmed/19181621
https://www.hifo.uzh.ch/research/jessberger/publications/Jessberger2009LM.pdf
https://core.ac.uk/display/53600034
http://whoville.ucsd.edu/PDFs/446_Jessberger_etal_LearnMem_2009.pdf
http://europepmc.org/articles/PMC2661246
https://hdl.handle.net/11379/33616
Rights: CC BY NC
Dokumentencode: edsair.doi.dedup.....4d7f24dc69d7ca10aca910d5b43bd61c
Datenbank: OpenAIRE
Beschreibung
Abstract:New granule cells are born throughout life in the dentate gyrus of the hippocampal formation. Given the fundamental role of the hippocampus in processes underlying certain forms of learning and memory, it has been speculated that newborn granule cells contribute to cognition. However, previous strategies aiming to causally link newborn neurons with hippocampal function used ablation strategies that were not exclusive to the hippocampus or that were associated with substantial side effects, such as inflammation. We here used a lentiviral approach to specifically block neurogenesis in the dentate gyrus of adult male rats by inhibiting WNT signaling, which is critically involved in the generation of newborn neurons, using a dominant-negative WNT (dnWNT). We found a level-dependent effect of adult neurogenesis on the long-term retention of spatial memory in the water maze task, as rats with substantially reduced levels of newborn neurons showed less preference for the target zone in probe trials >2 wk after acquisition compared with control rats. Furthermore, animals with strongly reduced levels of neurogenesis were impaired in a hippocampus-dependent object recognition task. Social transmission of food preference, a behavioral test that also depends on hippocampal function, was not affected by knockdown of neurogenesis. Here we identified a role for newborn neurons in distinct aspects of hippocampal function that will set the ground to further elucidate, using experimental and computational strategies, the mechanism by which newborn neurons contribute to behavior.
ISSN:15495485
10720502
DOI:10.1101/lm.1172609