The rodent object-in-context task: A systematic review and meta-analysis of important variables

Milou S. C. Sep; Marijn Vellinga; R. Angela Sarabdjitsingh; Marian Joëls

doi:10.1371/journal.pone.0249102

Peer Review History

Original SubmissionMarch 9, 2021
19 Apr 2021 Decision Letter - Patrizia Campolongo, Editor PONE-D-21-07607 Measuring context-dependent memory in rodents: a systematic review and meta-analysis of important variables in the object-in-context task. PLOS ONE Dear Dr. Sep, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Both reviewers liked the manuscript and suggested minor revisions which will improve the already high quality of the paper. Please address all comments and submit your revised manuscript by Jun 03 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. 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The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf 2. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ****** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Sep et al. wrote an interesting systematic review and metanalysis on the object-in-context task in mice and rats, to identify critical variables, including strain, sex, experimental manipulations, differences in the behavioral paradigm, etc., that might influence the outcome of the task. Based on their analyses the authors found that, among all variables examined, the sex, the scoring modality (manual vs automated), the size of the experimental arena, strongly influenced the behavioral outcome. The results obtained are very useful for informing future studies on context dependent memory performance. Overall the metanalysis is interesting and well performed, and, in general, the methodology and analyses are sound and the selection of data included in the study is mostly clear. My concern is related to the scarce information on the experimental group included in the study. Authors assert that naive, sham-operated or saline-injected rodents were included and that data were extracted taking into consideration the three types of control groups. However, for the saline-injected controls, for example, it would have been interesting to also consider as a variable the time of injection with respect to the behavioral paradigm (e.g. injection before the sample phase, injection before the test phase, etc.), as it is known that the injection itself might induce a stress response (Rao et al., 2012 Biol Psychiatry 72(6):466-75) which influences memory performance. Indeed authors in their metanalyses observed an inverted U-shaped dependency for prior arousal, with highest DR values in moderately aroused animal. This limitation should be mentioned in the discussion. Reviewer #2: This is a systematic review that provide an up-to-date overview and the protocol-related variations in the object-in-context task for rodents. The method and the data analysis used in this analytical review is undoubtedly adequate and knowing the factors that influence the performance of a task is important for the generalization of results between research groups. In this sense, the following suggestions would help to support this analytical review. 1. The Introduction needs a hypothesis. An analytical review also needs a hypothesis or at least a prognostic. In the Discussion you mention on two occasions that you already expected the observed results (p. 18), but in the Introduction, it is not mentioned why these results are expected. 2. Change “Methodological considerations section” from the Discussion section to the Method section, it is more appropriate in the Method section. 3. Include a likely explanation of how the highlighted factors affect behavior. In the Discussion these factors are only mentioned in a descriptive way. For example, sex and age. I understand that your objective was to look for factors that influence the behavior of the task, but that could already be inferred by just reviewing the literature. A tentative explanation would help for the originality of the manuscript and its justification. 4. I think you can omit from the title of the manuscript “Measuring context-dependent memory in rodents” since their work only represents results obtained from the analysis of “object-in-context task”. 5. Mention the factors that you identify that affect the task in the Abstract, instead of just mentioning that somewhere in the article you are going to give recommendations. I think this will help the reader to know if it is an article of interest. ****** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: Yes:** Gina L. Quirarte [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. 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Revision 1
1 Jun 2021 Author Response Responses to general comments When submitting your revision, we need you to address these additional requirements. 1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf We have updated the manuscript according to these guidelines. 2. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. We have checked the references; no papers have been retracted. No changes to the references list were required. Responses to Review Comments Reviewer #1: Sep et al. wrote an interesting systematic review and metanalysis on the object-in-context task in mice and rats, to identify critical variables, including strain, sex, experimental manipulations, differences in the behavioral paradigm, etc., that might influence the outcome of the task. Based on their analyses the authors found that, among all variables examined, the sex, the scoring modality (manual vs automated), the size of the experimental arena, strongly influenced the behavioral outcome. The results obtained are very useful for informing future studies on context dependent memory performance. Overall the metanalysis is interesting and well performed, and, in general, the methodology and analyses are sound and the selection of data included in the study is mostly clear. My concern is related to the scarce information on the experimental group included in the study. Authors assert that naive, sham-operated or saline-injected rodents were included and that data were extracted taking into consideration the three types of control groups. However, for the saline-injected controls, for example, it would have been interesting to also consider as a variable the time of injection with respect to the behavioral paradigm (e.g. injection before the sample phase, injection before the test phase, etc.), as it is known that the injection itself might induce a stress response (Rao et al., 2012 Biol Psychiatry 72(6):466-75) which influences memory performance. Indeed authors in their metanalyses observed an inverted U-shaped dependency for prior arousal, with highest DR values in moderately aroused animal. This limitation should be mentioned in the discussion. We agree with the reviewer that saline-injections before the sample and test phase could have differential effects, as it is known that arousal/stress can affect memory formation and retrieval differently [1]. As our primary aim was to summarize which variations in the object-in-context task affect its outcomes, we did not perform subgroup analysis (e.g. saline-injected animals alone), or focus on the sources of variation within each factor (e.g. time of injection within a control type). We aim to provide an overview that future studies can use to determine which variables need further exploration. Time of injection within saline-injected animals could be such a factor, although the relatively low variable importance of ‘control type’ (bottom 50%, figure 6) suggests that variation from this source has limited effects on overall performance. We have addressed this point on p 19 of the discussion: “Of note, it is also known that arousal and stress can affect memory formation and retrieval differently [1]. As a consequence, the time of saline-injection -which can trigger a mild stress response [2]- with respect to the OIC phases (e.g. before sample or test phase; or exactly when relatively to the test phase) could have caused variation in the saline-injected control animals, which was not accounted for in the current meta-analysis. However, type of control group ranked among the less important variables (bottom 50%), suggesting that variation from this source might have limited effects on overall performance.” Reviewer #2: This is a systematic review that provide an up-to-date overview and the protocol-related variations in the object-in-context task for rodents. The method and the data analysis used in this analytical review is undoubtedly adequate and knowing the factors that influence the performance of a task is important for the generalization of results between research groups. In this sense, the following suggestions would help to support this analytical review. 1. The Introduction needs a hypothesis. An analytical review also needs a hypothesis or at least a prognostic. In the Discussion you mention on two occasions that you already expected the observed results (p. 18), but in the Introduction, it is not mentioned why these results are expected. Our expectation was that the implementation and interpretation of the OIC would vary considerably across studies and that some of these variations would affect animals’ performance. We have added our expectation to the introduction (p5): “Considerable variation in OIC implementation among published studies is expected, and we expect that (some of) these variations affect animals’ performance.” And adjusted the discussion accordingly (p15): “As expected, a substantial part (37.5%) of the variance could be explained by a set of moderators identified by a random forest approach, …” We had no prior hypotheses about specific variables, and we agree with the reviewer that the use of ‘as expected’ in the previous version of the discussion was therefore incorrect. In the previous version of the manuscript ‘as expected’ was used to indicate that observations aligned with literature, not as reference to our a priori hypothesis. We have adjusted phrasing in the discussion accordingly: (p18): “In line with frequently reported sex-dependence of spatial or neutral contextual memory formation across species [3,4], male animals showed a higher DR than females, but firm conclusions await more studies in females.” (p19): “Smaller arenas resulted in higher DR values, as did large difference between context A and B.” 2. Change “Methodological considerations section” from the Discussion section to the Method section, it is more appropriate in the Method section. We thank the reviewer for this suggestion. As the paragraph provides a reflection on the methodological strengths and limitations of the complete, performed analyses we feel it is best placed in the discussion. We agree that the section title can be confusing, and we have changed the title to “methodological strengths and limitations”. 3. Include a likely explanation of how the highlighted factors affect behavior. In the Discussion these factors are only mentioned in a descriptive way. For example, sex and age. I understand that your objective was to look for factors that influence the behavior of the task, but that could already be inferred by just reviewing the literature. A tentative explanation would help for the originality of the manuscript and its justification. We agree with the reviewer that elaboration on these factors would benefit the manuscript. We have added a reflection on age: (p 18): “ This is of interest, since context-dependent memory in humans shows a similar inverted U-shaped age-dependency [5]. Memory context-dependency increases with age in children, as they develop the ability to bind and integrate information [6]. As adults get older, context dependency decreases, which has been linked to age-related reductions in selective attention -leading to hyper-binding of too much contextual details thereby reducing accuracy for the relevant context- [7,8]; alterations in prefrontal-hippocampal connectivity [9]; and declines in hippocampal neurogenesis [10,11].” And sex: (p18): “In line with frequently reported sex-dependence of spatial or neutral contextual memory formation across species [3,4], male animals showed a higher DR than females, but firm conclusions await more studies in females. Performance in the OIC might be enhanced in males compared to females, as the former are more likely to adopt a hippocampus-dependent place-strategy to navigate an environment (i.e. navigate based on a contextual map) than the latter (who are more likely to use a striatum-dependent landmark strategy) [12]. Such place-strategies could create a stronger representation of the OIC context in the brain, enabling richer context-dependent memories.” 4. I think you can omit from the title of the manuscript “Measuring context-dependent memory in rodents” since their work only represents results obtained from the analysis of “object-in-context task”. We agree with the reviewer, we have changed the title to “The rodent object-in-context task: a systematic review and meta-analysis of important variables”. We have also changed the short title to “Meta-analysis of the rodent object-in-context task” 5. Mention the factors that you identify that affect the task in the Abstract, instead of just mentioning that somewhere in the article you are going to give recommendations. I think this will help the reader to know if it is an article of interest. We have added these variables to the abstract: “Based on these observations we provide recommendations on sex, strain, prior arousal, context (size, walls, shape, etc.) and timing (habituation, learning, and memory phase) to create more consensus in the set-up, procedure and interpretation of the object-in-context task for rodents” References 1. Quaedflieg CWEM, Schwabe L. Memory dynamics under stress. Memory. 2018;26: 364–376. doi:10.1080/09658211.2017.1338299 2. Rao RP, Anilkumar S, Mcewen BS, Chattarji S. Glucocorticoids Protect Against the Delayed Behavioral and Cellular Effects of Acute Stress on the Amygdala. BPS. 2012;72: 466–475. doi:10.1016/j.biopsych.2012.04.008 3. Andreano JM, Cahill L. Sex influences on the neurobiology of learning and memory. Learn Mem. 2009;16: 248–266. doi:10.1101/lm.918309 4. Keeley RJ, Bye C, Trow J, Mcdonald RJ. Strain and sex differences in brain and behaviour of adult rats: Learning and memory, anxiety and volumetric estimates. Behav Brain Res. 2015;288: 118–131. doi:10.1016/j.bbr.2014.10.039 5. Sep MSC, Joëls M, Geuze E. Individual differences in the encoding of contextual details following acute stress: An explorative study. Eur J Neurosci. 2020; ejn.15067. doi:10.1111/ejn.15067 6. Imuta K, Scarf D, Carson S, Hayne H. Children’s learning and memory of an interactive science lesson: Does the context matter? Dev Psychol. 2018;54: 1029–1037. doi:10.1037/dev0000487 7. Powell PS, Strunk J, James T, Polyn SM, Duarte A. Decoding selective attention to context memory: An aging study. Neuroimage. 2018;181: 95–107. doi:10.1016/j.neuroimage.2018.06.085 8. Strunk J, James T, Arndt J, Duarte A. Age-related changes in neural oscillations supporting context memory retrieval. Cortex. 2017;91: 40–55. doi:10.1016/j.cortex.2017.01.020 9. Ankudowich E, Pasvanis S, Rajah MN. Age-related differences in prefrontal-hippocampal connectivity are associated with reduced spatial context memory. Psychol Aging. 2019;34: 251–261. doi:10.1037/pag0000310 10. Kirschen GW, Ge S. Young at heart: Insights into hippocampal neurogenesis in the aged brain. Behav Brain Res. 2019;369: 111934. doi:10.1016/j.bbr.2019.111934 11. Alam MJ, Kitamura T, Saitoh Y, Ohkawa N, Kondo T, Inokuchi K. Adult neurogenesis conserves hippocampal memory capacity. J Neurosci. 2018;38: 6854–6863. doi:10.1523/JNEUROSCI.2976-17.2018 12. Yagi S, Galea LAM. Sex differences in hippocampal cognition and neurogenesis. Neuropsychopharmacology. 2019;44: 200–213. doi:10.1038/s41386-018-0208-4 Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0249102.r002
25 Jun 2021 Decision Letter - Patrizia Campolongo, Editor The rodent object-in-context task: a systematic review and meta-analysis of important variables PONE-D-21-07607R1 Dear Dr. Sep, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Patrizia Campolongo Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0249102.r003
Formally Accepted
8 Jul 2021 Acceptance Letter - Patrizia Campolongo, Editor PONE-D-21-07607R1 The rodent object-in-context task: a systematic review and meta-analysis of important variables Dear Dr. Sep: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Patrizia Campolongo Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0249102.r004

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