Validation of Automated Learning and Memory Tests in

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					                                                               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
                  Abstract                                                                                                   Results

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
lesion animals.

          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.
                                                                                                                                                                                                              Conclusions

                                                                                                                                                                                      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