Talk:WikiJournal of Medicine/The Hippocampus

WikiJournal of Medicine/The Hippocampus

Submission letter

The main authors, who will be displayed at the top of the article, first need to agree with the conditions of of WikiJournal of Medicine/Submission letter for single author as adapted to this article in the box below. Agreement can be done by adding:

• I agree with the submission letter above ~~~~

at the bottom of this section. If there are any conflicts of interest, please describe the nature of them. You may edit the text in the box accordingly. Mikael Häggström (discuss • contribs) 20:11, 9 October 2016 (UTC)

I hereby affirm that I am an author of the Hippocampus article in Wikipedia.

I agree to have my real name displayed in the work when published in WikiJournal of Medicine.

I affirm that the article content is not already submitted to a publisher that prohibits further publication.

I acknowledge that I cannot withdraw this agreement, and that the content may or may not be kept permanently on a Wikimedia project.

Conflicts of interest:

• My institution has not at any time received payment or services from a third party for any aspect of the submitted work.
• I do not have financial relationships, regardless of amount of compensation, with entities in the bio-medical arena that could be perceived to influence, or that give the appearance of potentially influencing, what I wrote in the submitted work. This includes all sources of revenue paid, or promised to be paid, directly to me or my institution on my behalf over the 36 months prior to submission of the work.
• I do not have patents, whether planned, pending or issued, broadly relevant to the work.
• There are no other relationships or activities that readers could perceive to have influenced, or that give the appearance of potentially influencing, what I wrote in the submitted work.

• "I agree with the submission letter above" --Iztwoz (discuss • contribs) 21:50, 10 October 2016 (UTC)

Comments from first peer reviewer

The article has now been peer reviewed by an neuroscientist (Ph.D.) independent from the journal administration, and who preferred to remain anonymous. I copy the comments to the box below, with permission. Mikael Häggström (discuss • contribs) 19:35, 11 November 2016 (UTC)

Also, the peer reviewer has "no conflicts of interest in reviewing this work". Mikael Häggström (discuss • contribs) 13:45, 24 December 2016 (UTC)

Review by anonymous peer reviewer ,
These assessment comments were submitted on 24 Dec 2016, and refer to this previous version of the article

This is a often simplistic and outdated review of the state of our knowledge about the hippocampus. It can be improved significantly by following some general recommendations:

1. The notion of the "limbic system" is outdated. Yes the hippocampus is connected with areas involved in emotion, but no one talks about a limbic system any more. Connections with areas involved with emotion is a relatively small focus of work on the hippocampus these days.

2. The roles of the hippocampus in memory and navigation as described make no effort to reconcile the obvious disconnect between hippocampal involvement in declarative memory versus spatial navigation, which despite the efforts of many to ignore it, is an obstacle to understanding what the hippocampus does. If readers are to me away with any reasonable understanding of this disconnect, the author should address it directly - see, for example, Schiller et al. J Neurosci. 2013 35:13904 and Buzsaki & Moser Nature Neurosci 2013 16:130.

3. A large literature on functional imaging studies of the role of the hippocampus in memory is ignored. Any reasonable treatment on hippocampal function in memory must include this very important area of research. Appropriate overage of this area, which is at least as important as the large section on the evolution of the hippocampus,for example, will highlight the need to reconcile the roles of the hippocampus in memory and navigation.

4. The author seems a bit confused about what areas constitute the hippocampus - most include the dentate and subiculum. I know this depends on how strict one is in using the term Ammon’s horn, but really, get up to date.

Response

Let me respond to these points.

1. The term "limbic system" is arguably outdated but it is still very widely used. "No one talks about a limbic system any more" is absurd. A Google Scholar search for articles with "limbic system" in their title finds 249 published since the year 2010. I don't believe the way it is used in the Wikipedia article is harmful.

2. It is not the role of a Wikipedia article to reconcile discrepancies, only to describe them and discuss attempts that have been made to reconcile them. The article does that to at least some degree, although it could be updated.

3. This is a valid point. The Wikipedia article was largely written in 2008 and 2009, and much of this literature has appeared since then. I'm not sure that I'll be able to find the time or motivation to take care of this, though.

4. As far as I can tell the literature itself is confused on this point. The article gives the definition that is used in most anatomy books. If there are sources strong enough to justify changing this, I would welcome a pointer to them.

The basic issue here is that this article has received so little attention since I took it through the FA process that I'm not really very motivated to do a lot of work on it. Best regards, Looie496 (discuss • contribs) 14:23, 8 December 2016 (UTC)

Thanks for your replies. So, the main issue that needs to be addressed before inclusion of the article in the journal is the disconnect between hippocampal involvement in declarative memory versus spatial navigation, preferably by mentioning functional imaging studies. The peer reviewer has referred to the following works:

• Schiller, D.; Eichenbaum, H.; Buffalo, E. A.; Davachi, L.; Foster, D. J.; Leutgeb, S.; Ranganath, C. (2015). "Memory and Space: Towards an Understanding of the Cognitive Map". Journal of Neuroscience 35 (41): 13904–13911. doi:10.1523/JNEUROSCI.2618-15.2015. ISSN 0270-6474. 
• Buzsáki, György; Moser, Edvard I (2013). "Memory, navigation and theta rhythm in the hippocampal-entorhinal system". Nature Neuroscience 16 (2): 130–138. doi:10.1038/nn.3304. ISSN 1097-6256. 

The article has now undergone amendments from these peer review comments: [1]. Upon checking with the peer reviewer, the following issues were raised. Mikael Häggström (discuss • contribs) 13:50, 24 December 2016 (UTC)

Review by anonymous peer reviewer ,


1. The approach-avoidance conflict section overemphasizes one publication that does not reflect a major area of research on the hippocampus and is just confusing to consider along with memory and spatial cognition. Remove it. I suspect the findings of this paper reflect memory, not emotional function.

2. There is no evidence that the spatial function of the hippocampus evolved earlier than its memory function. Indeed, a more parsimonious account is that memory is an evolutionary adaptation that supports spatial navigation, among other less well studied behaviors, and the emphasis on space reflects a bias in the research paradigms of investigators more so than a dedicated function of the hippocampus.

Further amendments by the author are located at [2]. Subsequent comment by peer reviewer follows. Mikael Häggström (discuss • contribs) 13:50, 24 December 2016 (UTC)

Review by anonymous peer reviewer ,


Memory is pervasive, and is employed in many applications, including approach-avoidance conflicts, navigation, and many many more challenges in our everyday lives. Highlighting these two applications can mislead readers to think the hippocampus is dedicated to these applications rather than appropriately thinking of them as among an enormous range of situations where we employ memory.

Response

Response copied from Wikipedia:Talk:Hippocampus#Issues in recent peer review
Hi Mikael Häggström I think the first points raised are covered in the 'Later research' para in the Functions section. Also the comments in the review of 2016 in Approach-avoidance conflict also covers this view. And I see this newer research as very relevant to the page. The section on navigation does have the heading Spatial memory and navigation. ? Shall not be making any more edits now. Happy holidays --Iztwoz (talk) 16:28, 24 December 2016 (UTC)

Author response is located at Wikipedia:Talk:Hippocampus#Issues in recent peer review (possibly archived). Mikael Häggström (discuss • contribs) 17:42, 26 December 2016 (UTC)

Comments from 2nd peer reviewer

Review by anonymous peer reviewer ,
These assessment comments were submitted on 26 Jan 2017, and refer to this previous version of the article

I have "no conflicts of interest in reviewing this work".

A very excellent work. Must have taken huge efforts to get the article in this great shape. Here are some suggestions that might improve the article.

1. First of all Images need to have an outline frame that include the comments below it. Because at the time being it is a little bit confusing to have a sentence or a paragraph at the beginning of each section that seems to come out of no where. I think over the long run the journal would have a pdf version so, the illustrations need to be named e.g. fig. 1 MRI coronal view .....etc. For example, in page 5, section 1.4 "role in spatial memory" in the pdf section of the article there is a paragraph at the start that the reader starts reading it then finds difficulty linking it to the next paragraph. Then one would figure that the paragraph is actually a comment on the image and not the starting paragraph.

2. Images need to be redistributed and linked directly to the text. We aim to have a journal i.e. would be cited. So images must be numbered, cited inside article, and relevant to the text, for example the image in section 7 "Other animals" showing the drawing by Camillo Golgi .......etc, would be better to be positioned under the section 2 "Name" as the image is of historical value and section 2 is the part mentioning historical issues.

3. Images better to make them black&White printers friendly. Although colored printers are now widespread, but a slight improvement in image might make them balk & white friendly. This would help using the articles of the journal by a more widespread population. For example the first image in the article, section 1 "Abstract" when printed in black & white, the hippocampus would not be visible, putting an outline around it or a black arrow would help.

4. It might be helpful to add some images - if possible - to the article. Few suggestions:

4.1. Image showing comparing Hippocampus of humans, a vertebrate, birds.

4.2. The image of the Hippocampal formation schematic! need more improvement. The text is too small, it hardly can be read.

4.3. The image at begainingof section 4.2 Role in spatial memory and navigation need adding a description in the comment that colors indicate different stiulation patterns, otherwise a black & white version would be not totally illustrative.

1. Adding another EEG image might be beneficial to illustrate EEG findings of section 5.1 Theta rhyth.

5. A lot of specific terminologies need to be put in italics or in between quotation marks. This method would help readers coming to know new knowledge and terminologies e.g. "place cells". This methodology was used in some terminologies in the article as in section 5.1 "Theta rhythm". But in the majority of text, all specific terminologies need to be put in italic or in between quotation marks. For example: Limbic system, Place cells, Long term potentiation, The Knowledge (page 6), trisynaptic circuit, medial pallium, lateral pallium and mushroom bodies.

6. Listed below in bold and italics are some suggestions to improve the article:

6.0. In Dementia of Alzheimer type, the hippocampus is one of the first regions of the brain to suffer damage; memory loss and disorientation are included among the early symptoms. Damage to the hippocampus can also result from oxygen starvation (hypoxia), encephalitis, or medial temporal lobe epilepsy. People with extensive, bilateral hippocampal damage may experience anterograde amnesia (the inability to form and retain new memories).

6.1. In rodents as model organisms, the hippocampus has been studied extensively as part of a brain system responsible for spatial memory and navigation. Many neurons in the rat Latin name and mouse Latin name hippocampus respond as place cells: that is, they fire bursts of action potentials when the animal passes through a specific part of its environment. Hippocampal place cells interact extensively with head direction cells, whose activity acts as an inertial compass, and conjecturally with grid cells in the neighboring entorhinal cortex.

6.2. The earliest description of the ridge running along the floor of the temporal horn of the lateral ventricle comes from the Venetian anatomist Julius Caesar Aranzi (1587), who likened it first to a silkworm Latin name and then to a seahorse (Latin: hippocampus from Greek: ἵππος, "horse" and κάμπος, "sea monster"). The German anatomist Duvernoy (1729), the first to illustrate the structure, also wavered between "seahorse" and "silkworm." "Ram's horn" was proposed by the Danish anatomist Jacob Winsløw in 1732; and a decade later his fellow Parisian, the surgeon de Garengeot, used "cornu Ammonis" – horn of (the ancient Egyptian god) Amun,[4] who was often represented as having a ram's head.[5] Its abbreviation CA is used nowadays in naming hippocampus subfields.

6.3. Another reference appeared with the term pes hippocampi, which may date back to Diemerbroeck in 1672, introducing a comparison with the shape of the folded back forelimbs and webbed feet of the mythological hippocampus (Greek: ἱππόκαμπος), a sea monster with a horse's forequarters and a fish's tail. The hippocampus was then described as pes hippocampi major, with an adjacent bulge in the ocipital horn, the calvar avis, being named pes hippocampi minor.[4] The renaming of the hippocampus as hippocampus major, and the calcar avis as hippocampus minor, has been attributed to Félix Vicq-d'Azyr systematising nomenclature of parts of the brain in 1786. Mayer mistakenly used the term hippopotamus in 1779, and was followed by some other authors until Karl Friedrich Burdach resolved this error in 1829. In 1861 the hippocampus minor became the centre of a dispute over human evolution between Thomas Henry Huxley and Richard Owen, satirised as the Great Hippocampus Question. The term hippocampus minor fell from use in anatomy textbooks, and was officially removed in the Nomina Anatomica of 1895.[6] Today, the structure is just called the hippocampus,[4] with the term cornu Ammonis surviving in the names of the hippocampal subfields Cornu Ammonis abbreviation CA is used nowadays in naming subfields CA1–CA4.[7]

6.4. In terms of anatomy, the hippocampus is an elaboration of the edge of the cerebral cortex, of the medial temporal lobe.[8] The cortex thins from six layers to the three or four layers that make up the hippocampus. This is also seen as an infolding of archicortex into the temporal lobe that can only be seen in dissections.[9] The set of structures that line the edge of the cortex make up the limbic system (Latin limbus meaning border): These include the hippocampus, cingulate cortex, olfactory cortex, and amygdala. Paul MacLean introduced the term limbic system in 19?? and later suggested that the limbic structures comprise the neural basis of emotion. The hippocampus is anatomically connected to parts of the brain that are involved with emotional behavior—the septum, the hypothalamic mammillary body, and the anterior nuclear complex in the thalamus, and is generally accepted to be part of the limbic system.[10]

6.5. The hippocampus, including the dentate gyrus, has the shape of a curved tube, which has been compared to a seahorse, and a ram's horn (Cornu Ammonis) hence the subfields CA1, CA2, CA3, and CA4 adding a clear illustration would be beneficial.[8] It can be distinguished as an area where the cortex narrows into a single layer of densely packed pyramidal neurons, which curl into a tight U shape. One edge of the "U," – CA4, is embedded into the backward-facing, flexed dentate gyrus. The hippocampus is described as having an anterior and posterior part (in primates) or a ventral and dorsal part in other animals. Both parts are of similar composition but belong to different neural circuits.[14] In the rat, the two hippocampi resemble a pair of bananas, joined at the stems by the commissure of fornix (also called the hippocampal commissure). In primates, the part of the hippocampus at the bottom, near the base of the temporal lobe, is much broader than the part at the top. This means that in cross-section the hippocampus can show a number of different shapes, depending on the angle and location of the cut.

6.6. Several other connections play important roles in hippocampal function.[8] Beyond the output to the EC, additional output pathways go to other cortical areas including the prefrontal cortex. A major output goes via the fornix to the lateral septal area and to the mammillary body of the hypothalamus (which the fornix interconnects with the hippocampus).[9] The hippocampus receives modulatory input from the serotonin, norepinephrine, and dopamine systems, and from the nucleus reuniens of the thalamus to field CA1. A very important projection comes from the medial septal area, which sends cholinergic and GABAergic fibers (GABA=Gamma amino butyric acid) to all parts of the hippocampus. The inputs from the septal area play a key role in controlling the physiological state of the hippocampus; destruction of the septal area abolishes the hippocampal theta rhythm and severely impairs certain types of memory.[17]

6.7. Since at least the time of Ramon y Cajal (1852 – 1934) , psychologists have speculated that the brain stores memory by altering the strength of connections between neurons that are simultaneously active.[82] This idea was formalized by Donald Hebb in 1948,[83] but for many years thereafter, attempts to find a brain mechanism for such changes failed. In 1973, Tim Bliss and Terje Lømo described a phenomenon in the rabbit hippocampus that appeared to meet Hebb's specifications: a change in synaptic responsiveness induced by brief strong activation and lasting for hours or days or longer.[84] This phenomenon was soon referred to as long-term potentiation, abbreviated LTP. As a candidate mechanism for memory, LTP has since been studied intensively, and a great deal has been learned about it.

6.8. The hippocampus is a particularly favorable site for studying LTP because of its densely packed and sharply defined layers of neurons, but similar types of activity-dependent synaptic change have now been observed in many other brain areas.[85] The best-studied form of LTP occurs at synapses that terminate on dendritic spines and use the neurotransmitter glutamate. Several of the major pathways within the hippocampus fit this description and exhibit LTP.[86] The synaptic changes depend on a special type of glutamate receptor, the NMDA receptor, which has the special property of allowing calcium to enter the postsynaptic spine only when presynaptic activation and postsynaptic depolarization occur at the same time.[87] Drugs that interfere with NMDA (N-methyl-D-aspartate) receptors block LTP and have major effects on some types of memory, especially spatial memory. Genetically modified mice that are modified to disable the LTP mechanism, also generally show severe memory deficits.[87]

6.9. Age-related conditions such as Alzheimer's disease (for which hippocampal disruption is one of the earliest signs[88]) have a severe impact on many types of cognition, but even normal aging is associated with a gradual decline in some types of memory, including episodic memory and working memory (or short-term memory). Because the hippocampus is thought to play a central role in memory, there has been considerable interest in the possibility that age-related declines could be caused by hippocampal deterioration.[89] Some early studies reported substantial loss of neurons in the hippocampus of elderly people, but later studies using more precise techniques found only minimal differences.[89] Similarly, some MRI studies have reported shrinkage of the hippocampus in elderly people, but other studies have failed to reproduce this finding. This phrase needs paraphrasing to make it more easier to understand: There is, however, a reliable relationship between the size of the hippocampus and memory performance — meaning that not all elderly people show hippocampal shrinkage, but those who do tend to perform less well on some memory tasks.[90] There are also reports that memory tasks tend to produce less hippocampal activation in the elderly than in the young.[90] Furthermore, a randomized control trial published in 2011 found that aerobic exercise could increase the size of the hippocampus in adults aged 55 to 80 and also improve spatial memory.[91]

6.10. Title of section 6.2 would better be named as Stress and hypercortisoliemia

6.11. The hippocampus contains high levels of glucocorticoid receptors, which make it more vulnerable to long-term stress than most other brain areas.[92] Stress-related steroids affect the hippocampus in at least three ways: first, by reducing the excitability of some hippocampal neurons; second, by inhibiting the formation of new neurons in the dentate gyrus; third, by causing atrophy of dendrites in pyramidal cells of the CA3 regionreference. There is evidence that humans having experienced severe, long-lasting traumatic stress show atrophy of the hippocampus more than of other parts of the brain.[93]

6.12. Sex-specific responses to stress have also been demonstrated to have an effect on the hippocampus. During situations in which adult male and female rats were exposed to chronic stress the females were shown to be better able to cope need to state the direct effect on hippocampus.[99]

6.13. Epilepsy: The hippocampus is often the focus of epileptic seizures: hippocampal sclerosis is the most commonly visible type of tissue damage in temporal lobe epilepsy.[100] It is not yet clear, however, whether the epilepsy is usually caused by hippocampal abnormalities or whether the hippocampus is damaged by cumulative effects of seizures.[101] In experimental settings where repetitive seizures are artificially induced in animals, hippocampal damage is a frequent result. This may be a consequence of the hippocampus's being one of the most electrically excitable parts of the brain. It may also have something to do with the fact that the add tis sentence to the introduction section at the start of the article: hippocampus is one of very few brain regions where new neurons continue to be created throughout life.[102]

6.14. The hippocampus has been seen as central to the pathology of schizophrenia, both in the neural and physiological effects.[103] It has been generally accepted that there is an abnormal synaptic connectivity underlying schizophrenia. Several lines of evidence implicate changes in the synaptic organization and connectivity, in and from the hippocampus[103] Many studies have found dysfunction in the synaptic circuitry within the hippocampus and its activity on the prefrontal cortex. The glutamergic pathways (explain more which pathways) have been seen to be largely affected. The subfield CA1 is seen to be the least involved of the other subfields,[103][107] and CA4 and the subiculum have been reported elsewhere as being the most implicated areas.[107] The review concluded that the pathology could be due to genetics, faulty neurodevelopment or abnormal neural plasticity. It was further concluded that schizophrenia is not due to any known neurodegenerative disorder.[103]

7. A small explanation need to be added to "Hebbian synaptic changes", although it has a distinct Wiki link, but it needs a breif comment inside the article text in section 5.2 Sharp waves.

8. it may be helpful to add abbreveations in one paragraph before the article notes.

9. It would be beneficial to all readers to add some summering tables to the sections:

• 4.2 Role in spatial memory and navigation
• 4.4 Hippocampal regions
• 5.2 Sharp waves

10. an extra space is present before section 4.4 Hippocampal regions.

11. section 4.4 Hippocampal regions might be better to be moved before the sections about hippocampus functions i.e. start of section 4.0 Functions.

12. The Wiki journal of Medicine need to state clearly the target readers of its article.

13. I assume that the article was checked for plagiarism.

The article represents an addition to medical literature. Good luck--Ashashyou (discuss • contribs) 04:33, 26 January 2017 (UTC)

updated review --Ashashyou (discuss • contribs) 11:03, 29 January 2017 (UTC)

Response

Have done what I can in response to reviewer's comments. A few are still in the realms of formatting and may need editorial approving. The use of italics when items are already linked is one example. Another is the suggestion of making a separate section to include abbreviations used.

Re the images suggestion - can only use from available images and there are none I can find in birds for example.

Otherwise have dealt with most of the reviewer's suggestions - thank you. Re the use of Hypercortisolemia in heading - not usual to include medical term in heading especially when its not actually referred to in text. As for using summary tables - personally I am not prone to use tables. The information is concentrated as it is, in my view, and difficult to summarise. I did make several changes in the hope of easier reading. Thank you --Iztwoz (discuss • contribs) 21:08, 8 February 2017 (UTC)

Editorial response

Many of these points relate to the layout system of the journal, which does not apply only to this article. An "Editorial response" is not usually required, but I feel it is very useful here.

1. The PDF file of the final article will be tailored to the content (See guidelines on this step), and not be the automatically generated one in the left menu.

I will bring some to the editorial board, to discuss whether we should generally recommend these measures:

2. Whether we should recommend that images must be numbered, and be cited inside article.

3. Black & White friendliness

12. Target readers

13. Plagiarism checking of wiki content. It is problematic due to false positives created by the various mirror sites.

Mikael Häggström (discuss • contribs) 20:46, 3 February 2017 (UTC)

An update:

2. There is yet no consensus on whether images must be numbered, and be cited inside article, so until then, this way of formatting is permitted. Preferably, each image should be numbered as "Image 1" etc.

3. Black-and-white friendliness is now added to the guidelines [3]. I arranged to have arrows added to the mentioned image in the introduction.

12. The target readers of WikiJournal are now added at its About page [4]

13. There still exists no convenient way to perform plagiarism checking of content from Wikipedia due to the false positives in existing systems.

Mikael Häggström (discuss • contribs) 20:23, 12 February 2017 (UTC)

Response to update

Many thanks to the editors and to the author for their kind work on updates. Glad to see all the improvements of the article.

As stated before, the article provides an added value to scientific literature. It is fit for publishing.

Some few suggestions if possible:

• I have uploaded some images (all newly uploaded except the first image, not upladed by me) that might help in making better demonstration for the article. They are all creative common license and in the commons wikimedia. In differnet categories. They are just a suggestion not an obligation. The author might chose whether or not to use them.
  • File:Golgi 1885 Plate XX.JPG ---A kitten Hippocampus (May be added to section 7 other animals)
  • File:Hippocampus-Hippocampal morphology of the four rodent species.jpg---Comparison of animals Hippocampus (May be added to section 7 other animals)
  • File:Hippocpus-Principal hippocampal subdivisions in the marmoset.jpg---Comparison of animals Hippocampus (May be added to section 7 other animals)
  • File:Hippocampus-Principal hippocampal cell number distribution in the phylogenetic tree.jpg---Comparison of animals Hippocampus (May be added to section 7 other animals)
  • File:Hippocampus-Hippocampal cell number and body weight relationships in the rodent group.jpg---Comparison of animals Hippocampus (May be added to section 7 other animals)
  • File:Hippocampus-Bird brain.png---A Bird brain Showing Hippocampus (HP) (May be added to section 7 other animals)
  • File:Hippocampus coronal section176157.fig.004.jpg ---Hippocampus and Cornu Ammonis regions (CA1, CA2, CA3, CA4) (May be added to section 3.1 circuitry or section 3 anatomy)
  • File:Hippocampal -Cornu Ammonis.png ---Cornu Ammonis in rats (May be added to section 7 other animals or section 3 anatomy or section 6.2 stress)
  • File:Epilepsy- right hippocampal seizure onset.png---An EEG showing Epilepsy-right hippocampal seizure onset (May be added to section 6.3 Epilepsy)
  • File:Epilepsy-left hippocampal seizure onset.png---An EEG showing Epilepsy-left hippocampal seizure onset (May be added to section 6.3 Epilepsy)

• As regard section 6.2 stress:
  • Glucocorticoids and increased cortisol level is the predominant idea discussed under this section and not stress.
  • Naming it only by the title STRESS may be slightly misleading. As stress include many many neuroendocrinal responses (e.g. glucocorticoids, epinephrine, norepnephrine, insulin, dopamine, ACTH ...etc). I find the section title stress, however the discussion inside the section has only discussed the glucocorticoids in most of the points raised inside (1st paragraph: Glucocorticoids receptors; 2nd paragraph: Chronic stress resulting in elevated levels of glucocorticoids; 2nd paragraph: The higher levels of cortisol in Cushing’s syndrome; 2nd paragraph: dendrites are shortened in length and reduced in number, in response to increased glucocorticoids; 2nd paragraph: After treatment with medication to reduce cortisol in Cushing’s syndrome).
  • Despite mentioning some general points of stress effect but mentioning the glucocorticoids was very evident, beside chosing not to talk about other neuroendocrine mediators related to stress. Mentioning the glucocorticoids occurred five times in this section and was discussed more extensive. However the good effect of neuroprotective ovarian hormones was added to the last sentence.
  • Actually Cushing syndrome (mentioned 3 times to demonstrate effect of glucocorticoids on Hippocampus) is a pathologic state of continuous elevated cortisol levels. I think if the title remains "STRESS", it should be removed from this section as it is not a state of stress. It is a pathologic state of hypercortisolemeia. It can be used to demonstrate effect of cortisol on Hippocampus but not the effect of stress on Hippocampus.
  • I think the title should include glucocorticoids or cortisol words. Otherwise few sentences about other neuroendocrine mediators related to stress may be added.
  • It is OK to include Medical terms in headings e.g. section 5.1 Theta waves, section 6.4 Schizophrenia & section 6.5 Transient global amnesia. It is a medical journal after all.

• As regard using the tables, it was a suggestion to improve the "yield" of the article to the readers and help to "take home messages". I can see that the article is very concentrated, that is why i have asked to point who are the target readers. Also i understand that the tables are "difficult to summerise" as you replied in your response. But we might need to put ourselves in the shoes of the reader. If it is difficult for a neuroscientist (as the author) to summerise a nice article like this, we would not expect high yield by the average reader or medical readers. After all it is a suggestion, you are free to accept or refuse.

As stated before, the article provides an added value to scientific literature. It is fit for publishing.

Good luck.--Ashashyou (discuss • contribs) 00:41, 22 February 2017 (UTC)

Preparation for PDF publication

On thing that will need to be sorted one way or another is the referencing format. Whilst a legitimate alternative on-wiki, unfortunately the "Short citations" system doesn't work well in the PDF without internal hyperlinks. For example, the inline short citation 129 in the Notes section is "Shettleworth, 2003", however none of the references in the Reference section name Shettleworth as an author so without the internal hyperlinks. My preference is making all of the references to inline citations, however an alternative is to ensure that all of the name-date citations are easily paired with a reference. Once this is sorted, I shall continue creating the formatted PDF (currently paused). T.Shafee(Evo﹠Evo)^talk 12:04, 11 March 2017 (UTC)