Abstract
The ability to associate memorized objects with their location in space gradually declines during normal aging and can drastically be affected by neurodegenerative diseases. This study investigates object-location paired-associates learning (PAL) in the grey mouse lemur (Microcebus murinus), a nonhuman primate model of brain aging. Touchscreen-based testing of 6 young adults (1–5 years) and 6 old adults (> 7 years) in the procedural rodent dPAL-task revealed significant age-related performance decline, evident in group differences in the percentage of correct decision during learning and the number of sessions needed to reach a predefined criterion. Response pattern analyses suggest decreased susceptibility to relative stimulus-position biases in young animals, facilitating PAL. Additional data from a subset of “overtrained” individuals (n = 7) and challenge sessions using a modified protocol (sPAL) further suggest that learning criteria routinely used in animal studies on PAL can underestimate the endpoint at which a stable performance is reached and that more conservative criteria are needed to improve construct validity of the task. To conclude, this is the first report of an age effect on dPAL and corroborates the role of mouse lemurs as valuable natural nonhuman primate models in aging research.
Highlights
The cognitive abilities of humans gradually change during aging, with different cognitive functions showing different age-related trajectories (e.g.1)
This study provides detailed performance data from the touchscreen-based rodent different PAL” (dPAL) protocol applied to a nonhuman primate model in aging-research, the grey mouse lemur
The here-presented data on paired-associates learning (PAL) in mouse-lemurs and our previous comparative study strongly suggest that conserved cognitive mechanisms underlie dPAL performance in animals from rodents to primates: While task acquisition rates have already been shown to be highly similar in young mouse lemurs, rats, and m ice[15], the here-presented data demonstrates that acquisition of the dPAL task in mouse lemurs is highly complex, involving the establishment and rejection of elemental response strategies at early stages and the dominance of a spatial strategy based on the recall of visuo-spatial paired-associates at asymptotic performance
Summary
The cognitive abilities of humans gradually change during aging, with different cognitive functions showing different age-related trajectories (e.g.1). Different from the CANTAB PAL test, the animal versions usually require repeated training and positive reinforcement for the animals to achieve high performance levels (e.g.11–15) Despite this conceptual difference, there is evidence for overlap in the brain areas involved in human CANTAB PAL and rodent dPAL, with a prominent role of hippocampal and medial prefrontal areas in both tasks (for a detailed overview see[5]). Exonic copy number variations in DLG2 have been suggested to be of pathogenic relevance in schizophrenia[18] and single nucleotide polymorphisms in this gene were linked to Alzheimer’s disease related increases in subcortical shape a symmetry[19] Regarding their sensitivity to age-related cognitive decline, little is known for the animal versions of the CANTAB PAL test.
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