Fig 1.
Schematic overview of the rodent object-in-context task (OIC).
During the sample phase (learning) an animal encounters a unique set of two objects in context A and next a different set in B. In the test phase (memory) the animal is exposed to either context A or B, with one object of each unique set.
Fig 2.
Flowchart of the study.
Fig 3.
Assessment of study quality (QA) and risk of bias.
The risk of bias according to SYRCLE’s risk of bias (RoB) tool [34], for each study, indicated by PubMed ID (PMID), included in the systematic review. The figure also shows if an a priori sample size calculation was performed and -if behavior was scored manually- an inter-observer rate was calculated. Unreported details were scored as an ‘unclear’ risk of bias.
Fig 4.
Forest plot visualizing the Discrimination Ratio (DR) per experimental group, per study; and the overall mean DR with 95% Confidence Interval. Studies are presented by publication year in ascending order.
Fig 5.
Funnel plot showing the DR of individual control groups on the x-axis against their standard errors (i.e., the square root of the sampling variances) on the y-axis. Vertical reference lines indicate the 0, i.e. no context-dependent memory; and the estimated overall mean DR based on the model. Colors indicate unique studies (PMID).
Fig 6.
Relative importance of potential moderators based on ‘permuted variable importance’ in the random forest-based meta-analyses.
Moderators above the horizontal line belong to the top 50%. Full definitions of variables and sum scores can be found in A2 and A5 Appendices in S1 File respectively.
Fig 7.
Partial dependence plots showing the predicted relation between DR and the upper half most important variables in the random forest-based meta-analysis, broken down by species: Mice in red vs. rat in blue.
The y-axis shows the predicted DR and x-axis shows the values of the variable that is named above the graph (in gray). The values of context.size A and B are shown in in cm2 and the values of time variables (learning. learning.delay, learning.time.trial, habituation.time.total.context, habituation.time.trial) are shown in minutes. Higher context.difference.score values indicate more different contexts and higher arousal.prior values indicate more arousal prior to the experiment. Strains values are abbreviations: TMm (Tg(Sim1cre)KH21Gsat/Mmucd mice), SEm (SEm Sv/Ev mice), ICm (ICR mice), BLm (C57BL/6 mice), LHr (Lister hooded rats), LEr (Long-Evans rats), SDr (Sprague-Dawley rats), Wr (Wistar rats), pDr (pigmented DA strain rats), DAr (Dark Agouti rats). DR.formula values are also abbreviations: n-f/t ((Tnovel-Tfamiliar)/(Tnovel+Tfamiliar)), n-f/t*100 ([(Tnovel-Tfamiliar)/(Tnovel+Tfamiliar)]*100), n/t ((Tnovel)/(Tnovel+Tfamiliar)), n/t*100 ([(Tnovel)/(Tnovel+Tfamiliar)]*100). The context.order value AA indicates that memory was tested in the context of the second learning trial, the value AB indicates that memory was tested in the context of the first learning trial, ‘both’ indicates that AA and AB were randomized. Finally, context.habituation.freq values show the number of visits per context. Full definitions of variables and sum scores can be found in A2 and A5 Appendices in S1 File respectively. Note, predictions based on the random forest-model do not take into account that strains belong to a specific species (either rat or mouse), hence rat and mice predictions were generated of all strains.
Fig 8.
Weighted scatter plots showing the distribution of the raw DR for the 50% most important variables in the random forest-based meta-analysis, broken down by species: Mice in red vs. rat in blue.
Dot size indicates the sample size of each observation. Most studies were performed in rats. The y-axis shows the mean DR and x-axis shows the values of the variable that is named below the graph. The values of context.size A and B are shown in in cm2 and the values of time variables (learning. learning.delay, learning.time.trial, habituation.time.total.context, habituation.time.trial) are shown in minutes. Higher context.difference.score values indicate more different contexts and higher arousal.prior values indicate more arousal prior to the experiment. Strains values are abbreviations: TMm (Tg(Sim1cre)KH21Gsat/Mmucd mice), SEm (SEm Sv/Ev mice), ICm (ICR mice), BLm (C57BL/6 mice), LHr (Lister hooded rats), LEr (Long-Evans rats), SDr (Sprague-Dawley rats), Wr (Wistar rats), pDr (pigmented DA strain rats), DAr (Dark Agouti rats). DR.formula values are also abbreviations: n-f/t ((Tnovel-Tfamiliar)/(Tnovel+Tfamiliar)), n-f/t*100 ([(Tnovel-Tfamiliar)/(Tnovel+Tfamiliar)]*100), n/t ((Tnovel)/(Tnovel+Tfamiliar)), n/t*100 ([(Tnovel)/(Tnovel+Tfamiliar)]*100). The context.order value AA indicates that memory was tested in the context of the second learning trial, the value AB indicates that memory was tested in the context of the first learning trial, ‘both’ indicates that AA and AB were randomized. Finally, context.habituation.freq values show the number of visits per context. Full definitions of variables and sum scores can be found in A2 and A5 Appendices in S1 File respectively.
Table 1.
Recommendations for future animal studies.