Talk:Neuromuscular junction

Untitled
Currently being revised for a Neuroscience class at Boston College as an assignment under The Society for Neuroscience by Greg Zandrow, Patrick Scherer and Olivia Hall. (11/3/12) — Preceding unsigned comment added by Zandrow (talk • contribs) 21:09, 3 November 2012 (UTC)

Assignment for The Society for Neuroscience/BI481 closed 12/3/12. Thank you for your patience. Zandrow (talk) —Preceding undated comment added 05:09, 3 December 2012 (UTC)

Not always ACh in invertebrates
The transmitter is not always ACh in invertebrates (http://jn.physiology.org/cgi/content/full/82/3/1477). Striedter 2005 ("Principals of Brain Evolution"), page 74 in fact states that, "... motor neurons use ... mainly (though not exclusively) glutamate in invertebrates".

Bayle Shanks 08:00, 7 August 2007 (UTC)

I added a note about the use of glutamatergic synapses in the crayfish.

Olivia Hall 5, Nov., 2012 —Preceding undated comment added 21:22, 5 November 2012 (UTC)

Bromage Score not relevant
As the given reference says, the Bromage Score "was designed to measure differences in [degree of motor block brought about by different] surgical blocks" - regional and neuraxial anaesthesia for surgery, as opposed to analgesia for obstetrics, which was the focus of the article. The effect of the local anaesthetic used in these circumstances is to prevent conduction of impulses in sensory and motor fibres, leaving the neuromuscular junction unmolested. The Bromage Score is not relevant to neuromuscular blockade and the section referring to it should be expunged - anyone disagree?Moletrouser (talk) 06:18, 7 September 2011 (UTC)

I agree that this section is not relevant to the neuromuscular junction, so I'm removing it from the page.

Olivia Hall 5 Nov., 2012 —Preceding undated comment added 21:24, 5 November 2012 (UTC)

Peer Review for BI481
This is an overall extremely well-detailed and well-spoken article that elaborates on many topics within the subject. I could definitely see myself using this article to help supplement class material, as it is so apprehensible and expanded. I also appreciate the inclusion of pictures in this article. The initial summary is very concise, giving just enough information to allow the reader to understand what the topic is without being too extensive.

I do really like the depth of the information included in the research methods section. It is notable that you went into detail about how ionophoresis was actually done rather than just listing it and its consequences. However, I noticed that it might be more complete to give the researchers full names, i.e. “Joel del Castillo” and “Bernard Katz”, the first time that they are mentioned in the article. This helps to avoid the awkwardness of the uncapitalized “del” that is currently beginning the sentence and provides an opportunity to link the names to their respective Wikipedia pages. Also, in the fourth line of the paragraph, “del” in the researcher’s name has been misspelled as “de”. Moreover, it might be most consistent to list their names in the same order throughout the paragraph.

You might consider swapping the placement of the development and research methods sections of the article. Then, you can include and elaborate upon the “knockout studies” portion in the research methods, lending to a more consistent organization and also allowing you to refer to the previous discussion of development. The phrase “Many other proteins also comprise the NMJ, and are required to maintain its integrity” in the development section seems extremely random, though perhaps an important topic on its own. I would either develop the idea more or take it out entirely.

I like how the mechanism of action was described in list-form. It makes the process much easier to follow and looks quite organized.

The “diseases” portion is really nicely elaborated, and the division of the diseases into “autoimmune” and “genetic” categories enhances reader understanding. Chavezmb (talk) 20:14, 18 November 2012 (UTC)

Thank you for pointing out the researcher name typos--we will make sure to fix them. We agree that switching the order of research methods and development makes sense, so we did that as well. We agree that the sentence regarding the NMJ structural proteins was vague, so we removed that--those proteins are discussed in the structure section. Thanks for the advice!! --OliviaHall10 (talk) 18:38, 2 December 2012 (UTC)

Peer Review for BI481
I like how detailed this article was on the neuromuscular junction. It touched all the main points brought up in class and much more. The list used for the mechanisms in the neuromuscular junction worked really well. It's easy to read, and concise. Moreover, I only saw one problem throughout the entire article. The MuSK receptor was defined earlier in Neuromuscular Junction section and then redefined again in Development of Neuromuscular Junction. I think it would be better if both definitions were combined and the MuSK receptor was defined once early in the article. Furthermore, I agree with everything stated in the above peer review.

Bellre (talk) 23:28, 18 November 2012

MuSK was only briefly mentioned in the first section, so we felt it necessary to elaborate in the second. Thanks for the suggestions!! --OliviaHall10 (talk) 18:45, 2 December 2012 (UTC)

Peer Review
Overall this is a really good article that is very well organized and clear, great job! Just a few pointers/grammatical errors to take note of. I'm going to go section by section to make it easier. In the introduction your first sentence needs a little editing, make sure you write is "a" synapse. Also you may want to consider talking about more general information about the neuromuscular junction in this section instead of the process of activation that occurs. Perhaps just simply stay that the neuromuscular junction is the path by which neurotransmitter travels to reach and activate the postsynaptic cell. The very difficult and tricky part about this article is finding the balance between information that belongs with this topic and information that belongs in a topic about Acetylcholine receptors or muscular activation. The next section on neuromuscular junction structure was very clear and well organized. I don't really have any pointers of things to change in this section, but I would like to add that I really enjoyed that you explained the terms you hyperlinked instead of just referring it to another page. This effectively makes the article much more clear and allows it to flow! For the next section on the structure of acetylcholine receptors I would consider moving the sentence about not all species having cholinergic neuromuscular junctions to after the part about the cys loop and structure. This will make the information more understandable as there are no breaks or interruptions. Also in the last paragraph you may want to describe that the Ach activating the metabotropic receptors on the presynaptic cell is excess Ach in the junction which can diffuse away. This is just to ensure that no false assumptions or conclusions are drawn from the article. I think in general you should describe the G protein deactivation of Ca+2 channels slightly more; just describe how the subunits are diffusing and directly acting on the channels. Without this information, the sentence may be slightly confusing for those with no background on the topic. Overall, the section on structure was very informative and well-written

The Research Methods section was also well-written. Just make sure you note that in the beginning you said del Castillo but then in the middle you said de Castillo, its probably just a spelling mistake! The section on development was very clear; it was very easy for me to understand despite not previously knowing any of that information. The only pointer I have is that you may want to explain how the Acetylcholine Receptors are getting from the central region of the muscle cell to the motor end plate. You effectively described why they become localized and all the associated proteins, it just seems like a small missing piece to the muscle. If this information is not actually proven scientifically yet, I would just note that research hasn't confirmed how this part is done, just so that you reference its presence. Also, I would not mention that there are many other proteins that are required to maintain its integrity, unless you are specifically going to name and talk about them. If anything, just name a few so that it doesn't seem as though you got lazy and skimmed past this part.

The section on associated diseases was very good, again I felt as though you included just enough information for it to be relevant but not step over in to the bounds of another wikipedia topic. There are a few grammatical errors/typos that you should watch out for. In the paragraph on LEMS you wrote that there is also usually a presence of a tumor, this just seems worded oddly to me. I would simply write that often times a tumor is present, or that those diagnosed with LEMS have also been diagnosed with having a tumor. Finally there were one or two extra parenthesis in between or around words, that is probably just a mistake in the edit page that didn't go through the way you wished. Just make sure you fix whatever the problem is for the final product! Finally, I think you should be careful about how information you include on the toxins as this may be too specific to AchR rather than the neuromuscular junction.

Overall a really great article, with just a few fixes here and there, you will have a polished final product! Great Job! Goldbejk (talk) 06:55, 19 November 2012 (UTC)

Thanks for your detailed review. We revised the introduction paragraph to cover more of our topic in general, but we kept the other information in because of its importance to the topic. We agree that the balance was difficult but we feel as though we have added enough information about ACh to give the readers the best understanding of the NMJ. We took everything you said about the structure section into consideration, and made the changes we felt necessary to the section. The typo regarding the del vs. de was fixed. The information regarding how ACh receptors get from the central region to the motor end plate is in the development section. The grammatical errors within the disease section are being fixed (Zandrow- have now been fixed the the best of our knowledge). Because the AChR is very prevalent in the NMJ, we found it fitting to discuss the effects on it due to toxins.--Schererp (talk) 18:46, 2 December 2012 (UTC)

Zandrow (talk)

Peer Review for BI481
Consider omitting specific, molecular level, function of the neuromuscular junction —i.e. the role of calcium and acetylcholine at the synapse—from the introduction paragraph. Without a more broad and introductory knowledge of the term, this may be confusing and incomplete. Rather, broad introduction to the various signaling pathways and their origins could be helpful.

It may help to very briefly compare the elements of the more typical CNS synapse while introducing elements of the neuromuscular junction’s structure. You may even want to explain why the variation exists. The first sentence of “Neuromuscular Junction” under STRUCTURE sort of supposes this. Then, however, there is little comparison. I think the MECHANISM OF ACTION section will be very helpful and informative. It may prove more helpful to appear earlier in the article.

The TOXINS section could be organized into categories of toxins based on how they act on the neuromuscular junction rather than “Botox” and “Snake Venom” alone.

Overall, the article contains a wealth of very thorough information. It will all prove more effective, however, with a little restructuring. In addition, I noticed some awkward phrasings and grammatical errors in a few places that can be easily fixed. James Kaberna Talk 17:30 19 November 2012

We kept the information regarding calcium and ACh in the introduction because we felt it was very important to the description of the NMJ as they are very important aspects of the topic. We did not compare the NMJ to synapses in the CNS because we did not find that overly relevant to the intended effect of the article. The Mechanism of Action section was moved up in the article. We disagree that the Toxins section should be organized differently because there are only two toxins highlighted. Thank you for your suggestions. --Schererp (talk) 18:51, 2 December 2012 (UTC)

Peer Review
Overall, this was an extremely detailed and well written article. As discussed in the above reviews, this article described in appropriate and relevant detail the neuromuscular junction and its structure, function, and its association with diseases. I would add, though, that in the first section (Structure: Neuromuscular Junction) I would briefly describe how the increased surface area caused by the invagination of the sarcolemma affects the ability of the junction to respond to certain stimuli and neurotransmitters. Also, in the "Knockout Studies" section, you conclude with the following statement: "Many other proteins also comprise the NMJ, and are required to maintain its integrity." I would either remove this particular sentence or possibly add a single other protein that constitutes the junction, as it leaves a bit to be desired and left me wondering what proteins these could actually be. For instance, a probable edit would be to include the previous sentence on mutations in Dok-7 in the sentence, so that it might read something like this: "Many other proteins also comprise the NMJ and are required to maintain its integrity, such as Dok-7. Mice deficient in Dok-7..." I would also have specified in the "Diseases" section which diseases can be inherited and which can be acquired, which you touched on in the opening paragraph of the section. You go on to sub-categorize the diseases section into "Autoimmune" and "Genetic," which is perfectly fine, but I would somehow incorporate into these sections which diseases are inherited and which are acquired, as I believe that would really bring the section together nicely. For instance, The Department of Veterinary Internal Medicine at the University of Saskatchewan found that acquired myasthenia gravis is a common disorder of the neuromuscular junction in dogs and cats, so something like this would have been a nice addition to the article here.

As far as grammatical errors go, I found very few, which speaks to the care you guys put into proofreading. I enjoyed reading the article and it provided extraordinary detail regarding the NMJ. Great job guys. Emmerlin (talk) 22:38, 19 November 2012 (UTC)

Thanks for the suggestions. Your first concern about the invagination of the sarcolemma is actually already mentioned in that section. We removed the sentence in question from the "Knockout Studies" section because we also found it vague. We did not discuss any epigenetic diseases, therefore we did not find it necessary to delineate between inherited and acquired. We are presently proofreading our article again for any grammatical errors (Zandrow- have now been fixed the the best of our knowledge). --Schererp (talk) 18:31, 2 December 2012 (UTC) Zandrow (talk) —Preceding undated comment added 05:02, 3 December 2012 (UTC)

Peer Review
Good job on your page. It is very detailed and informative. I just have a few suggestions that might be helpful in the editing process. In the section titled Acetylcholine Receptor maybe you could add a few words on what a “heteropentamer” is just to get a better sense of the structure. In the same section, the sentence, “This conformational change results in the increased affinity for a second ACh ligand in the second α subunit,” should be changed to “This conformational change results in the increased affinity for a second ACh ligand to bind to the second α subunit.” I think this change would avoid any confusion concerning the mechanism of Ach binding. In the last paragraph of this same section, perhaps you should consider linking or mentioning GPCRs (rather than just stating it is G-coupled) as I think that would be helpful to the Wikipedia community. The last sentence should end with something along the lines of “making it less likely to fire an action potential.” The research method section is concise and does a good job of explaining how researchers have designed experiments to localize and possibly quantify these receptors. A suggestion would be to maybe add a few words to explain what “coupling assayable enzymes” entails, so that others less knowledgeable can fully understand. The mechanism of action is a very useful section and I liked how it is step by step, which I think makes it very easy to follow along with. Other sections, such as the Disease section, were very good and very detailed. I think it was a good idea to include these relevant diseases. Overall, though, the language can get a little confusing for others less knowledgeable in the area, but as there were links to many of these disorders, it seems to be acceptable. One last suggestion would be to maybe incorporate the toxins section into the body of the article so that it is more relevant and easier to follow. For example, when the SNARE proteins are mentioned, maybe you could state that when they are interfered with by the botulinum toxin, paralysis ensues. That way the end of the article is the disease section, which makes sense. Overall, this is a very good article, it is well researched and thorough.MellaNatalie (talk) 22:56, 19 November 2012 (UTC)

Thanks for your suggestions. First, we elaborated on the heteropentamer specifics to make the structure of the AChR more clear. There is a section that discusses how muscarinic receptors are coupled with G-proteins; it also elaborates on the specific effects of those G-proteins. I'm not sure what else we should add to this. Also, we linked the words assayable enzyme to the enzyme assay page to avoid any confusion like you mentioned. We will move the toxins before the disease page; that is a good suggestion! Thanks! --OliviaHall10 (talk) 18:34, 2 December 2012 (UTC)

Peer Review
Great article guys. Very detailed and comprehensive explanation of the mechanism especially. It was good to break it up into steps to make it more accessible to the reader. One small thing I would change is the title of the Toxins section, to maybe "Effect of Toxins on Neuromuscular Junction", just to relate it back to the article. For the knock out studies, I would be less definitive about the findings, since they are not entirely established facts and still scientific speculations. Also the sentence "many other proteins also comprise the NMJ, and are required to maintain its integrity" is vague and doesn't really add anything to the section. Also maybe make mention of miniature end plate potentials as a result of quantal release, and it's contributions to the study and discovery of chemical transmission? Obviously very well presented article and useful to get a full molecular understanding of the NMJ.

See comments below regarding review. --Schererp (talk) 18:24, 2 December 2012 (UTC)

Peer Review
Great article guys. Very detailed and comprehensive explanation of the mechanism especially. It was good to break it up into steps to make it more accessible to the reader. One small thing I would change is the title of the Toxins section, to maybe "Effect of Toxins on Neuromuscular Junction", just to relate it back to the article. For the knock out studies, I would be less definitive about the findings, since they are not entirely established facts and still scientific speculations. Also the sentence "many other proteins also comprise the NMJ, and are required to maintain its integrity" is vague and doesn't really add anything to the section. Also maybe make mention of miniature end plate potentials as a result of quantal release, and it's contributions to the study and discovery of chemical transmission? Obviously very well presented article and useful to get a full molecular understanding of the NMJ. — Preceding unsigned comment added by ArmenAbagyan (talk • contribs) 23:11, 19 November 2012 (UTC)

We decided to keep the title of Toxins the same because we did not feel it was necessary to change it, and the proposed title seemed a bit too long for the section. We addressed the issue with the knock out studies and removed the sentence in question. The suggestion regarding the miniature end plate potentials was very helpful, and we will be adding that to our article. Thank you very much for the review. --Schererp (talk) 18:23, 2 December 2012 (UTC)

Peer Review
Hey guys, I'm going to start with suggestions for your article. In addition to fixing general grammatical errors throughout the article (such as "also known as a muscle cells" in your introduction), you can condense your introduction by eliminating redundancies such as "or junction" and spending less time discussing the basics of neurotransmitter release following an action potential. Instead, you should discuss the other neurotransmitters involved at this junction, as ACh is not the only type of neurotransmitter. Moreover, instead of listing the steps in the mechanism of action section, you can make this section flow better by actively showing how each step relates to the preceding step. The mechanism section could also be more detailed: for example, how exactly do vesicles dock in the cell membrane and what types of SNARE proteins facilitate this docking?

You do not need a subsection called "knockout studies" under the section of "development of the neuromuscular junction." Knockout studies are very common and this subsection can be inserted at the beginning (or end) of the neuromuscular junction development section by simply saying something along the lines of the following: "Mice with knockout agrin or MuSK genes do not display the formation of a neuromuscular junction. In addition, formation of ACh receptor clusters were not observed in mice deficient in Dok-7 proteins." In general, this section can also be improved with a further discussion of how Dok-7 induces the "clustering" of ACh receptors.

In the section regarding Botox, you should talk more about the mechanism of action (general mechanism is sufficient) of how botulinum toxin interferes with SNARE proteins and connect this mechanism to the resulting inhibition of ACh release. Again, I think small grammatical errors are a must-fix, as there are a significant number of them throughout the article.

The "structure" section was definitely a strength of this article, especially the part discussing how ACh receptors become localized to postjunctional folds. Overall, I enjoyed reading the article, especially about the various autoimmune disorders attributed to a deficiency of the neuromuscular junction.

Kwakda (talk) 01:52, 20 November 2012 (UTC)

Thanks for the suggestions. First, we reworked the introductory paragraph, as we agreed that it was vague and slightly redundant. Next, I don't think that we necessarily need to elaborate into the specific mechanism of the SNARE proteins. It begins to get outside of the scope of this article, so we think that saying neurotransmitter release from vesicles via SNARE protein interactions is sufficient (we linked to the SNARE proteins wikipedia page). We added the knockout section to the development section, as we agree that it fits better there. The mechanism for AChR clustering by Dok-7 is not known at this time, per your request to elaborate. We added to the botulinum toxin section to elaborate on the mechanism of action. Thanks for your help! --OliviaHall10 (talk) 18:26, 2 December 2012 (UTC)

Review
First off be careful of how you word things. In your first paragraph some of the ways you describe the connection of the neuron to the fiber isn't the best way to word that connection. As well, some of the grammar throughout your page is off. Also, although you may have learned some of the things you stated in this article in your classes, whatever you put on this page and state as a fact needs to be cited. It may be difficult for some things but if you can find a good review, that can take care of most of the basic thing that should be cited. This is especially true for sections such as "research methods." and mechanism of action. The knockout section seems a bit out of place in this page. This should just be part of one of the previous sections as it doesn't have enough work to be its own section, nor important enough. It should be placed under what it showed through the study. Otherwise good job with the thorough sections, it's a good read. AdamMJenks (talk) 03:26, 29 November 2012 (UTC)

We rephrased the introductory paragraph; we agree that some of the wording was vague. Also, we added the knockout section sentences to development section; it seems to fit better there. As far as the citations in the "research methods" and "mechanism of action sections," we counted over 10 references, so I'm not sure why there is a problem there. Thanks for the suggestions! --OliviaHall10 (talk) 18:15, 2 December 2012 (UTC)

We have edited this article for grammatical errors and phrasing problems. To the best of our knowledge they have all been addressed. Thank you for you input. Zandrow (talk) —Preceding undated comment added 05:42, 3 December 2012 (UTC)