Aβ1-42 Oligomer Injection Model: Understanding Neural Dysfunction and Contextual Memory Deficits in Dorsal CA1
Round 1
Reviewer 1 Report
Comments and Suggestions for Authors
Major comments:
This review is well-organized, with a clear structure and a concise summary of the subject. However, the section titled "Conclusions" is limited to a single paragraph. This is particularly noteworthy given the comprehensive nature of the study. To enhance the comprehensibility and impact of the paper, the authors should consider expanding this section to encompass all the key logical points of their work.
Minor comments:
Overall:
- Remove the transposition of the word “effects” from the title.
- In Figure 1B, the pointers from the captions are preferably black.
Line-by-line comments:
Lines 36-37: “a rise in the level of Aβ” “even without the formation of amyloid plaques” - the words appear to be written in a different font
Author Response
Please see the attachment.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Comments and Suggestions for Authors
The subject of this review is an important topic that highlights the significance of the most toxic form of Aβ, soluble oligomers pathology in specific brain areas at specific ages to study the associated cognitive functions. However, I have some concerns about the title, abstract, and introduction, therefore, the manuscript requires revision.
Authors discussed the one-trial task-based training associating the context with the aversive stimulus (emotional), which seems stress-induced learning, and other limbic regions are highly involved. Besides inhibitory avoidance learning, the hippocampal CA1 majorly been studied mainly for other spatial learning (eg, line 186) and working memory behavior, such as Morris water maze, Barnes maze, Radial arm maze, etc. Therefore, I think the title of the MS could be changed- instead of “contextual IA” to “CA1-dependent cognitive deficits in AD.” Authors could add other non-aversive spatial learning tasks relevant to AD.
Line 45, More importantly, the presence of amyloid plaques may not account for memory deficits. This sentence can be improved. "Merely amyloid plaque (without oligomers)"
Lines 151-168, the Ventral CA1 part could be removed as it does not fit with the main topic of this review.
Line 172: ventral CA1 has a higher amyloid plaque burden than its dorsal pole [42]. What does it mean? What behavior is related to the ventral CA1 area that is affected in AD? Whether ventral CA1-associated behavior has been tested in AD.
Line 170-173, Citation [42], this study has been performed by using transgenic models (5xFAD and 3xTg), thus they studied overall amyloid deposition, and differences were noticed in aged groups, not at early AD. Additionally, this study suggested the ventral part of CA (CA1 and CA3) is subject to a heavier pathological/amyloid burden than their dorsal parts. Whereas, the current review focuses on dorsal CA1 and related contextual learning and memory.
Line 196, Sentence can be improved by adding “After receiving shock in the dark-region of the box, if the animals have……
Fig 3, Fig legend: Could you describe the details of the IA task or cite the article where the details of the method are described? For example, during the training, after receiving the shock, was the door open to escape the shock or closed? And how long was the animal in this chamber, all 30 min? As fear-extension plays a major role, it’s very important to mention such details.
Also, please mention, preferably in the picture, that no electric foot shock was delivered during the test.
Could authors cite more articles than their own showing foot shock behavior applied to study memory deficits in AD models or associated with Aβ plaque pathology?
Author Response
Please see the attachment.
Author Response File: Author Response.pdf
