Validation of Automated Learning and Memory
Tests in Mice Using Hippocampal Lesions
Priestley M, Beraki S, Shamloo M
Stanford Behavioral and Functional Neuroscience Laboratory,
Stanford Institute for Neuro-Innovation and Translational Neurosciences
Lesions in C57BL/6J mice were used to Delayed Match-to-Place IntelliCage PhenoTyper
validate two automated behavioral tests, the Mice were subjected to a Morris water maze task designed The IntelliCage platform is an automated behavior The PhenoTyper is an automated behavioral apparatus
PhenoTyper and the IntelliCage. Data from to assess cognitive flexibility, i.e. the ability to deal with assessment system used for monitoring different aspects of used to monitor continuous locomotor activity over an
these two tests support findings from earlier an increasingly demanding cognitive task. Animals were behavior in mice living in social groups with minimal extended period of time. Animals were housed
reports showing that these lesions lead to given 4 trials/day for 7 days with the escape platform human interference. The IntelliCage consists of four individually and monitored via an infrared camera in
deficits in behavioral performance in the moving to a new location at the beginning of each day. corners where access to water can be made to depend on the roof of the chamber. Each animal was allowed 3
Delayed Match-to-lace (DMP) water maze The animals had to learn that the platform position was individual learning performance. The system registers the days of habituation to the cage followed by 3 days of
task. DMP was used to assess cognitive changed between days but stayed in the same position activities of all individuals separately, since they all carry baseline activity.
flexibility, where the mice had to cope with the during any given day. subcutaneous ID-chips, and the entrance to each corner is
Lesioned mice showed hyperactivity both in a novel
fact that the platform position stayed in the equipped with a radio antenna.
environment and after having been well habituated to
same position during the course of a day but Lesioned animals showed a deficit in acquiring this task.
the arena. Lesioned animals also demonstrated
was changed between days. Hippocampal Short term memory for spatial information was impaired In the place learning experiment, both groups showed
increased velocity during habituation.
lesion animals were significantly impaired in in the hippocampal lesion animals as revealed by a lack of equal learning curves. However, upon reversal, the
this task, evident from less improvement improvement from trial 1 to trial 2. Moreover, spatial lesioned animals performed with a significantly higher
between trials. Short term memory for spatial long-term memory, which was measured by the error rate. The lesioned animals also showed a delay in
information appeared to be impaired in the improvement from trial 1 to trial 4, was significantly finding the water in the Intellicage and hyperactivity
hippocampal lesion animals as revealed by impaired in the hippocampal lesion animals. during habituation to the novel environment.
lack of improvement between two consecutive
trials. The rapid consolidation of spatial .
memory to long-term memory was also
significantly impaired in the hippocampal
Methods & Materials
Hippocampal lesions were performed by
applying an infusion of NMDA (N-methyl-D-
aspartic acid) (5mg/ml) into four sites in each
hemisphere. Sham-control mice were treated
identically, but no acid was applied. Animals
were tested in the Delayed Match-to-Place,
IntelliCage, and PhenoTyper behavioral tests.
The purpose of this experiment was to validate our
automated learning and memory tests of animal
behavior. This study has shown that the PhenoTyper
and IntelliCage tests can be used to assess behavioral
and cognitive tasks modulated by the hippocampus. In
the future, the behavioral and cognitive effects of
mouse models of neuro-cognitive disorders could be
evaluated using these different approaches.
Special Thanks to the Stanford Institute of Neuro-innovation and Translational
Neuroscience, Nay Saw, Mehrdad Faizi, Angelo Encarnacion, Donna Molaie,
Josie Valenzuela, Patick Bader, Christine Htun, and Jackie Pham