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

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 strat...

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Vydáno v:Learning & memory (Cold Spring Harbor, N.Y.) Ročník 16; číslo 2; s. 147
Hlavní autoři: Jessberger, Sebastian, Clark, Robert E, Broadbent, Nicola J, Clemenson, Jr, Gregory D, Consiglio, Antonella, Lie, D Chichung, Squire, Larry R, Gage, Fred H
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.02.2009
Témata:
Animals
Animals, Genetically Modified
Dentate Gyrus - cytology
Dentate Gyrus - growth & development
Dentate Gyrus - physiology
Food Preferences
Form Perception - physiology
Genetic Vectors
Lentivirus - genetics
Male
Maze Learning - physiology
Memory - physiology
Neurons - physiology
Psychomotor Performance - physiology
Rats
Rats, Sprague-Dawley
Recognition, Psychology - physiology
Social Environment
Space Perception - physiology
Stereotaxic Techniques
Wnt Proteins - genetics
Wnt Proteins - physiology
ISSN:1549-5485, 1549-5485
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Shrnutí: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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ISSN:1549-5485
1549-5485
DOI:10.1101/lm.1172609