title: Large-scale phenotyping links adult hippocampal neurogenesis to the reaction to novelty.
abstract: The discovery of adult-born neurons in the hippocampus has triggered a wide range of studies that link the new neurons to various behavioral functions. However, the role of new neurons in behavior is still equivocal. Conflicting results may be due to the difficulty in manipulating neurogenesis without off-target effects as well as the statistical approach used, which fail to account for neurogenesis-independent effects of experimental manipulations on behavior. In this study, we apply a more comprehensive statistical and conceptual approach. Instead of between-group analyses, we consider the within-group relationships between neurogenesis and behavior (ANCOVA and mediation analysis) in a large-scale experiment, in which distinct age- (3 and 5 months) and strain- (DBA and C57) related differences in basal levels of neurogenesis in mice are compared with a large number (∼1,500) of behavioral read outs. The analysis failed to detect any association between anxiety and motor impulsivity with neurogenesis. However, within-group adult hippocampal neurogenesis is associated with the reaction to novelty. Specifically, more neurogenesis is associated with a longer latency to explore and a lower frequency of exploratory actions, overall indicative of a phenotype where animals with more neurogenesis were slower to explore a novel environment. This effect is observed in 5-months-old, but not in 3-months-old mice of both strains. An association between the reaction to novelty and adult neurogenesis can have a major impact on results from previous studies using classical behavioral experiments, in which animals are tested in a--for the animal--novel experimental set-up. The neurogenesis-novelty association found here is also a necessary link in the relation that has been suggested to exist between neurogenesis and psychiatric disorders marked by a failure to cope with novelty.
authors.affiliation: Institute of Anatomy, University of Zürich, Switzerland.|Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zürich, Switzerland.|Institute of Human Movement Sciences and Sport, Department of Health Sciences and Technology, ETH Zurich, Zürich, Switzerland.
authors.forename: R Maarten
authors.initials: RM
authors.lastname: van Dijk
authors.affiliation: In Silico Lead Discovery, Novartis Institutes for Biomedical Research, Basel, Switzerland.
authors.forename: Stanley E
authors.initials: SE
authors.lastname: Lazic
authors.affiliation: Institute of Anatomy, University of Zürich, Switzerland.
authors.forename: Lutz
authors.initials: L
authors.lastname: Slomianka
authors.affiliation: Institute of Anatomy, University of Zürich, Switzerland.|Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zürich, Switzerland.|Institute of Human Movement Sciences and Sport, Department of Health Sciences and Technology, ETH Zurich, Zürich, Switzerland.
authors.forename: David P
authors.initials: DP
authors.lastname: Wolfer
authors.affiliation: Institute of Anatomy, University of Zürich, Switzerland.|Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zürich, Switzerland.
authors.forename: Irmgard
authors.initials: I
authors.lastname: Amrein
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D002452:Cell Count; D000089622:Doublecortin Domain Proteins; D005106:Exploratory Behavior / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D010641:Phenotype; D011930:Reaction Time / Q000502:physiology
chemical_list: D000089622:Doublecortin Domain Proteins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides
keywords: IntelliCage; anxiety; behavior; exploration; mouse