PONE-D-23-13004Environmental enrichment improves social isolation-induced memory impairment:  The possible role of ITSN1-Reelin-AMPA receptor signaling pathwayPLOS ONE

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- https://www.sciencedirect.com/science/article/abs/pii/S0016648020303944?via%3Dihub

https://karger.com/dne/article-abstract/44/6/547/835246/Reduced-Reelin-Expression-Induces-Memory-Deficits?redirectedFrom=fulltext

https://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0127945

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KERKER received research grant from Department of Science & Technology (EMR/2016/005217 dt.21.03.2018)

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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: No

Reviewer #2: Yes

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: N/A

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

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Reviewer #1: No

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

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Reviewer #1: No

Reviewer #2: No

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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: A large body of literature has reported that enriched environments can ameliorate behavioral impairments caused by social isolation, including memory loss, so this study is less innovative. In addition, there are many defects in the Introduction, Methods, and Disscusssion, specific comments are as follows.

1. The writing quality of this manuscript needs to improve. For instance, in the Introduction Section, the authors need introduce the published work of social isolation-induced memory impairment as well as the ameliorating effect of environmental enrichment on social isolation-induced behavioral impairment. In the Discussion Section, the authors also need compare their finding with the previous published papers.

2. The description of animals in groups is not clear. How many animals in each group are kept in a cage and how many cages in each group? What principles are used to screen mice for behavioral, pathological, and molecular analysis? It is suggested that the author draw an experimental flow chart.

3. The resolution of the picture is too low. In particular, the symbols in the picture are difficult to distinguish. In addition, the layout of the pictures should be further optimized, such as Figure 3 and Figure 4 can be arranged in a page.

4. The statistical method, the meaning of the corresponding symbol in the figure, and the number of animals in each group should be indicated in the figure legends.

5. The authors also should make clear the reasons for the selection of male animals and for observing the hippocampus.

Reviewer #2: This study uses wild-caught mus booduga to investigate how environmental enrichment and social isolation alter many hippocampal molecular markers linked to synaptic transmission and neuronal excitability as well as impact cognitive performance. Overall, the experiments and well-performed, the analysis and statistics are robust. Some improvements are needed for the materials and methods, as well as improvements in figure readability. Importantly, correction needs to be made for the grammar errors throughout the text.

Please provide more details about the experimental methods, specifically the caging conditions:

- What bedding was used for all of the caging conditions?

- “How much is “plenty of food and water.” Ab libitum? Please specify

- “Healthy” mice were used. How much did they weigh? How was health assessed?

Please provide more detail about the scoring and analysis of the behavioral videos. How was the timing recorded? What software was used?

Please provide a definition of measures of working memory and reference memory in the methods.

Please provide title for the figures, this will enhance readability.

Figure 1 – Please provide explanation in the figure legend for the meaning of DW, STSC, LTSC and EE. Also, which test is being performed here?

Figure 2 – the bands are very dark- in the copy I have downloaded I can barely see the SYT4 and BDNF signals over the dark background.

Figure 4 – the background signal is very bright,, I cannot see the labelling well at all. Could higher-quality images please be provided? Also, the scale bars are illegible.

Figure 5 – same problem for figure 2.

Figure 8 – the text in panels a and b is illegible. TOO SMALL. Please adjust the figure so that normal sized font can be used.

There are many grammatical errors throughout the manuscript. I highly recommend using a grammar-checking program to improve the text.

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Reviewer #1: No

Reviewer #2: No

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Environmental enrichment improves social isolation-induced memory impairment:  The possible role of ITSN1-Reelin-AMPA receptor signaling pathway

PONE-D-23-13004R1

Dear Dr. K.E. Rajan 

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.

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Michelle Melgarejo da Rosa

Academic Editor

PLOS ONE