Not all water mazes are created equal: Cyclin D2 knockout mice with constitutively suppressed adult hippocampal neurogenesis do show specific spatial learning deficits

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

Studies using the Morris water maze to assess hippocampal function in animals, in which adult hippocampal neurogenesis had been suppressed, have yielded seemingly contradictory results. Cyclin D2 knockout (Ccnd2-/-) mice, for example, have constitutively suppressed adult hippocampal neurogenesis but had no overt phenotype in the water maze. In other paradigms, however, ablation of adult neurogenesis was associated with specific deficits in the water maze. Therefore, we hypothesized that the neurogenesis-related phenotype might also become detectable in Ccnd2-/- mice, if we used the exact setup and protocol that in our previous study had revealed deficits in mice with suppressed adult neurogenesis. Ccnd2-/- mice indeed learned the task and developed a normal preference for the goal quadrant, but were significantly less precise for the exact goal position and were slower in acquiring efficient and spatially more precise search strategies. Upon goal reversal (when the hidden platform was moved to a new position) Ccnd2-/- mice showed increased perseverance at the former platform location, implying that they were less flexible in updating the previously learned information. Both with respect to adult neurogenesis and behavioral performance, Ccnd2+/- mice ranged between wild types and knockouts. Importantly, hippocampus-dependent learning was not generally impaired by the mutation, but specifically functional aspects relying on precise and flexible encoding were affected. Whether ablation of adult neurogenesis causes a specific behavioral phenotype thus also depends on the actual task demands. The test parameters appear to be important variables influencing whether a task can pick up a contribution of adult neurogenesis to test performance. Cyclin D2 knockout mice with very low levels of adult hippocampal neurogenesis show specific learning deficits in the water maze task.

Details

Original languageEnglish
Pages (from-to)357-364
Number of pages8
JournalGenes, Brain and Behavior
Volume13
Issue number4
Publication statusPublished - Apr 2014
Peer-reviewedYes

External IDs

PubMed 24602283
ORCID /0000-0002-5304-4061/work/161408213

Keywords

Keywords

  • Adult neurogenesis, Cognitive flexibility, Dentate gyrus, Morris water maze, Pattern separation, Plasticity, Proliferation, Spatial learning, Stem cells, Strategies