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

By Sebastian Jessberger, R. E. Clark, Nicola J. Broadbent, Gregory D. Clemenson, A. Consiglio, D. C. Lie, L. R. Squire, Fred H. Gage. 2009

686 citations recorded by the source corpus.

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.

Subfields: Cellular and Molecular Neuroscience, Developmental Neuroscience, Neurology

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Citations in the corpus

New neurons and new memories: how does adult hippocampal neurogenesis affect learning and memory? (2010, positive): “Similar task-dependent involvement of hippocampal neurogenesis has been observed in other studies in both rats and mic”
Fragile X Mental Retardation Protein Regulates Proliferation and Differentiation of Adult Neural Stem/Progenitor Cells (2010, background): “More recent direct evidence has come from inducing the death of new neurons in the hippocampus [17–19] and from inhibiting the Wnt signaling pathway in the hippocampus using retrovirus [20].”
Prox1 Is Required for Granule Cell Maturation and Intermediate Progenitor Maintenance During Brain Neurogenesis (2010, background): “In mammals, neurogenesis occurs in the subgranular zone (SGZ) of the DG throughout adulthood [4,5,6,7]; this activity is thought to be the basis for the acquisition of new memories [3,8,9].”
Emerging roles of Wnts in the adult nervous system (2010, background): “and decreases long-term retention of spatial and object recognition memory in adult rat”
Prospero-related homeobox 1 gene (Prox1) is regulated by canonical Wnt signaling and has a stage-specific role in adult hippocampal neurogenesis (2011, background): “One of the key molecules expressed by local astrocytes within the neurogenic niche of the adult hippocampus is Wnt3, which is required for the generation of new granule cells (7, 32).”
Wnt-mediated activation of NeuroD1 and retro-elements during adult neurogenesis (2009, positive): “Recently, it was shown that Wnt-mediated adult hippocampal neurogenesis contributed to learning and memory in rat”
RBPJκ-Dependent Signaling Is Essential for Long-Term Maintenance of Neural Stem Cells in the Adult Hippocampus (2010, background): “…neurogenesis is important for hippocampus-dependent learning (Kee et al., 2007; Imayoshi et al., 2008; Clelland et al., 2009; Deng et al., 2009; Jessberger et al., 2009) and that impaired neurogenesis may contribute to hippocampal dysfunction observed in neuropsychiatric diseases such as…”
Adult-born hippocampal dentate granule cells undergoing maturation modulate learning and memory in the brain (2009, result): “For instance, similar to our findings, deficits in long-term spatial memory have been detected in rodents whose neurogenesis is greatly and permanently reduced by either irradiation or genetic manipulation (Snyder et al., 2005; Imayoshi et al., 2008; Jessberger et al., 2009).”
The role of adult hippocampal neurogenesis in brain health and disease (2018, background): “dependent memories, such as associating contexts with an aversive shock [71] or navigating to a hidden platform in the Morris water maze [65, 72].”