Abstract
Kleefstra syndrome is a disorder caused by a mutation in the EHMT1 gene characterized in humans by general developmental delay, mild to severe intellectual disability and autism. Here, we characterized cumulative memory in the Ehmt1+/− mouse model using the Object Space Task. We combined conventional behavioral analysis with automated analysis by deep-learning networks, a session-based computational learning model, and a trial-based classifier. Ehmt1+/− mice showed more anxiety-like features and generally explored objects less, but the difference decreased over time. Interestingly, when analyzing memory-specific exploration, Ehmt1+/− show increased expression of cumulative memory, but a deficit in a more simple, control memory condition. Using our automatic classifier to differentiate between genotypes, we found that cumulative memory features are better suited for classification than general exploration differences. Thus, detailed behavioral classification with the Object Space Task produced a more detailed behavioral phenotype of the Ehmt1+/− mouse model.
Highlights
Most if not all mental disorders are accompanied by memory deficits, with the quality of the deficit depending on the overlap between the underlying circuit needed for the respected memory type and the circuit affected by the disorder
Ehmt1+/− mice show decreased total exploration time (p = 0.004, detailed statistics in figure legend), this difference decreased over time
On a per-session level including all 21 trials, we have shown that Ehmt1+/− mice explore objects less and show increased memory expression, which is specific to our cumulative memory condition
Summary
Most if not all mental disorders are accompanied by memory deficits, with the quality of the deficit depending on the overlap between the underlying circuit needed for the respected memory type and the circuit affected by the disorder. It is harder to distinguish between semantic and episodic memories and in addition most commonly one-trial memory paradigms are used to assess memory deficits in disease. Such tasks, e.g. contextual fear conditioning or simple object in place memory, mainly test hippocampal processing (Squire et al, 2015). In the key condition of this task – overlapping – spatial configurations with two objects are presented to the animal over multiple trials per day, for four consecutive days This allows the animal to accumulate information over time in order to construct an abstracted, cumulative and perhaps semantic-like memory across training days. The additional advantage of this task is that it allows behavioral characterization beyond the memory measure, such as general movement patterns within an open field
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