The three-panel runway maze adapted to Microcebus murinus reveals age-related differences in memory and perseverance performances

Abstract

Microcebus murinus, a mouse lemur primate appears to be a valuable model for cerebral aging study and for Alzheimer's disease model since they can develop beta-amyloid plaques with age. Although the biological and biochemical analyses of cerebral aging are well documented, the cognitive abilities of this primate have not been thoroughly characterized. In this study, we adapted a spatial working memory procedure described in rodents, the sequential choice task in the three-panel runway, to mouse lemurs. We analyzed the age-related differences in a procedural memory task in the absence or presence of visual cues. Sixty percent of young adult and 48% of aged lemurs completed the exploratory, choice habituation and testing phases at the beginning of the procedure. Young adult lemurs showed a higher level of perseverative errors compared with aged animals, particularly in the presence of visual stimuli. Over trials, old animals made more reference errors compared to young ones that improved quickly their performances under random level. No significant improvement was observed in young adults and old ones over sessions. This study showed that behavioural performances of M. murinus assessed on the sequential choice task in the three-panel runway markedly differ from the previously reported abilities of rodents. The behavioural response of young adult lemurs was influenced by novelty-related anxiety that contributed to their performance in terms of perseverative errors. Conversely, aged lemurs showed less perseverative errors, a rapid habituation to the three-panel runway maze, but made more memory errors. Overall, these findings demonstrate the feasibility to use the three-panel runway task in assessing memory performance, particularly in aged mouse lemurs.

Figure 1

Whole behavioral procedure in the three-panel runway maze for lemurs. (A) Exploratory stage: two sliding gates are closed and one left open in each panel to allow the animals to exit the start box, explore the maze and retrieve the pear juice reward in the goal box. (B) Choice habituation: after successful exploration, all three sliding gates of the last panel are closed, i.e., in panel 4, then in panel 3 and 4, etc… (C) Testing phase: when animals successfully learned to push the sliding gates to pass through the next compartment for all 4 panels, specific pathways were randomly selected each day, like CBCA, and the two other gates in each panel blocked with front stoppers. Two procedures were followed with or without specific symbol drawn on the gates and associated with open (*) or closed (o) states. (D) Procedure: each session consisted in 6 trials per day, with inter-trial time interval of 2 min. The first trial was a sample trial in which animals learned the new combination of open gates each day and memory errors were recorded during the 5 last trials. Animals succeeding in performing the 6 trials during 5 consecutive sessions reached the inclusion criterion.

Figure 2

(A) Individual repartition of animals according to the different stages. Young and aged lemurs were tested in the procedure with or without symbols. The numbers in the pie charts indicated the numbers of animals reaching the different stages. Percentages over the whole population are shown within parentheses. No statistical significance was measured in repartitions for age and symbol (p > 0.05, Fisher’s exact test). Note that p = 0.08 for symbols between the two young groups. (B) Number of sessions to reach the inclusion criterion. The number of animals is indicated within the columns. ANOVA, F < 1 for age, F_(1,12) = 1.99, p > 0.05 for symbol, and F < 1 for the age x symbol interaction.

Figure 3

Exploratory time over trials in young and aged lemurs submitted to the three-panel runway test without symbols (A) or with symbols (B). Av: average of the data over the 5 test trials; * p < 0.05, ** p < 0.01 vs the first trial, Dunnett’s test; # p < 0.05, ## p < 0.01 vs young group in the same trial (Newman-Keuls’ test).

Figure 4

Evolution of perseverative errors (A, B), reference errors (C, D) and repetitive errors (E, F) over trials in young and aged lemurs submitted to the three-panel runway test. (A, C, E) procedure without symbols; (B, D, F) procedure with symbols. Av: average of the data over the 5 test trials. Repeated measure ANOVA; * p < 0.05, ** p < 0.01 vs the first trial, Dunnett’s test). # p < 0.05, ## p < 0.01, ### p < 0.001 vs young group in the same trial (Newman -Keuls’ test).