Automated dissection of permanent effects of hippocampal or prefrontal lesions on performance at spatial, working memory and circadian timing tasks of C57BL/6 mice in IntelliCage

Abstract

To evaluate permanent effects of hippocampal and prefrontal cortex lesion on spatial tasks, lesioned and sham-operated female C57BL/6 mice were exposed to a series of conditioning schemes in IntelliCages housing 8–10 transponder-tagged mice from each treatment group. Sequential testing started at 51–172 days after bilateral lesions and lasted for 154 and 218 days in two batches of mice, respectively. Spontaneous undisturbed behavioral patterns clearly separated the three groups, hippocampals being characterized by more erratic hyperactivity, and strongly impaired circadian synchronization ability. Hippocampal lesions led to deficits in spatial passive avoidance, as well as in spatial reference and working memory tasks. Impairment was minimal in rewarded preference/reversal schemes, but prominent if behavioral responses required precise circadian timing or included punishment of wrong spatial choices. No differences between sham-operated and prefrontally lesioned subjects in conditioning success were discernible. These results corroborate the view that hippocampal dysfunction spares simple spatial learning tasks but impairs the ability to cope with conflicting task-inherent spatial, temporal or emotional cues. Methodologically, the results show that automated testing and data analysis of socially kept mice is a powerful, efficient and animal-friendly tool for dissecting complex features and behavioral profiles of hippocampal dysfunction characterizing many transgenic or pharmacological mouse models.

Two-fold elevation of endogenous GDNF levels in mice improves motor coordination without causing side-effects

“…3e ). In the IntelliCage, mice were presented increasingly challenging learning and memory tasks known to be sensitive in animal models of impaired memory 59 , 60 . We found no differences in the percentage of incorrect visits with nose-pokes in four experimental designs assessing learning and memory: the corner preference (CP), serial reversal (SR), chaining (CHAIN) and patrolling (PATR) tasks (Suppl Fig.…”

Impact of Hyperhomocysteinemia and Different Dietary Interventions on Cognitive Performance in a Knock-in Mouse Model for Alzheimer’s Disease

“…The increase in the percentage of correct trials is in accordance with observations in a similar study [ 42 ]. In the IntelliCage setup [ 43 , 44 ], learning curves indicated a constant learning effect in the female WT animals.…”

“…We chose not to test males in the IntelliCage setup, because males are more prone to show aggressive behavior and hierarchical fighting, potentially resulting in injuries due to the housing of male mice in large groups. The IntelliCage tasks of learning ability cover a broad cognitive spectrum by combining the analysis of spatial memory with operant conditioning [ 43 ] and provide the advantage of being both home cage and behavioral test during the time of the experiment. Animals from all experimental groups lived together in the special cage for the period of about 7 weeks.…”

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“…Group data are presented as mean ± SD or mean ± SEM, the latter for behavioral time courses as specified in the respective figure legends. Data were analyzed with SPSS 25, GraphPad Prism 8.4, Origin Pro 2020, and IntelliCage Plus (TSE systems) and FlowR (XBehavior) 84 for IntelliCage experiments. Graphs were created in GraphPad Prism, SPSS, or FlowR; and they were arranged in Adobe Illustrator CC2020 and exported in TIFF format.…”