Related Experiment Video
Updated: May 2, 2026
The Double-H Maze: A Robust Behavioral Test for Learning and Memory in Rodents
Published on: July 8, 2015
Not all water mazes are created equal: cyclin D2 knockout mice with constitutively suppressed adult hippocampal
A Garthe1, Z Huang, L Kaczmarek
1German Center for Neurodegenerative Diseases (DZNE), Dresden, Germany; Center for Regenerative Therapies Dresden (CRTD), Dresden, Germany.
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.
Insights
Suppressed adult hippocampal neurogenesis in Cyclin D2 knockout mice did not cause general learning deficits. However, these mice showed impaired spatial precision and flexibility in the water maze task.
Area of Science:
- Neuroscience
- Behavioral Neuroscience
- Genetics
Background:
- Adult hippocampal neurogenesis plays a role in learning and memory.
- Studies on the behavioral impact of suppressed neurogenesis have yielded conflicting results.
- Cyclin D2 knockout (Ccnd2(-/-)) mice exhibit suppressed adult hippocampal neurogenesis without obvious deficits in standard water maze tests.
Purpose of the Study:
- To investigate if specific Morris water maze protocols can reveal behavioral deficits in Ccnd2(-/-) mice with suppressed adult hippocampal neurogenesis.
- To determine if the task demands influence the detectability of neurogenesis-related phenotypes.
- To characterize the precise nature of cognitive deficits, if any, in Ccnd2(-/-) mice.
Main Methods:
- Utilized the Morris water maze task with a specific protocol known to elicit deficits in mice with suppressed adult neurogenesis.
- Compared behavioral performance of Ccnd2(-/-) mice, Ccnd2(+/-) mice, and wild-type littermates.
- Assessed learning, spatial precision, strategy acquisition, and performance during goal reversal.
Main Results:
- Ccnd2(-/-) mice learned the task and showed goal quadrant preference but lacked precision in locating the exact platform position.
- These mice were slower in developing efficient search strategies and exhibited less flexibility during spatial reversal learning.
- Ccnd2(+/-) mice displayed intermediate phenotypes between wild-type and knockout mice.
- The deficits were specific to precise and flexible encoding, not general hippocampus-dependent learning.
Conclusions:
- The behavioral phenotype associated with suppressed adult hippocampal neurogenesis is dependent on task demands and specific test parameters.
- Ccnd2(-/-) mice demonstrate deficits in spatial precision and cognitive flexibility, highlighting the role of adult neurogenesis in these functions.
- Standard water maze protocols may not be sensitive enough to detect all neurogenesis-related cognitive impairments.
