PreprintCited by 654Neurogenesis and neuroplasticity mechanismsMemory and Neural MechanismsNeuroscience and Neuropharmacology Research

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

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Jessberger, Sebastian, Clark, Robert E., Broadbent, Nicola J., Clemenson, Gregory D., Consiglio, Antonella, Lie, D. Chichung, Squire, Larry R., Gage, Fred H.·2009·Learning & Memory

DOI 10.1101/lm.1172609PMC PMC2661246

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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.

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Authors: Jessberger, S., Clark, R. E., Broadbent, N. J., Clemenson, G. D., Consiglio, A., Lie, D. C., Squire, L. R., & Gage, F. H.
Affiliations: Salk Institute for Biological Studies (US)
University of California San Diego (US)
ORCID: Jessberger, Sebastian
Clark, Robert E.
Clemenson, Gregory D.
Consiglio, Antonella
Lie, D. Chichung
Squire, Larry R.
Gage, Fred H.
Venue: Learning & Memory
Publisher: Cold Spring Harbor Laboratory
Published: 2009-01-29
Volume: 16
Issue: 2
Pages: 147-154
ISSN: 1072-0502 (ISSN-L)
1549-5485
DOI: 10.1101/lm.1172609
PMC: PMC2661246
OpenAlex: W2148727841
Cited by: 654
References: 66
Citations by year: 2026: 9 · 2025: 22 · 2024: 20 · 2023: 29 · 2022: 28 · 2021: 30 · 2020: 46 · 2019: 28 · 2018: 30 · 2017: 44 · 2016: 48 · 2015: 42 · 2014: 53 · 2013: 60 · 2012: 46
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Learning & Memory (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (publishedVersion, cc-by-nc)
Site cant be reached (submittedVersion)
RECERCAT (Consorci de Serveis Universitaris de Catalunya) (submittedVersion, cc-by-nc)
Funders: National Science Foundation
U.S. Department of Veterans Affairs
James S. McDonnell Foundation
National Alliance for Research on Schizophrenia and Depression
National Institute on Aging (P50AG005131, P50-AG05131)
National Institute of Mental Health (P50 AG05131, AG05131, R01MH024600)
National Institute of Neurological Disorders and Stroke (R01NS050217, NS050217)
Topics: Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: adult neurogenesis, dentate gyrus, hippocampus, spatial memory, object recognition memory, Wnt signaling, lentiviral knockdown, social transmission of food preference, water maze
MeSH terms: Animals, Food Preferences, Form Perception, Genetic Vectors, Male, Memory, Neurons, Psychomotor Performance, Social Environment, Space Perception, Stereotaxic Techniques, Lentivirus, Rats, Sprague-Dawley, Maze Learning, Dentate Gyrus, Recognition, Psychology, Animals, Genetically Modified, Wnt Proteins, Rats

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

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