Talk:Excitatory synapse

Fast comments to Boston students

 * Please take a look at any article in Wikipedia (For example Parkinson's disease, written mainly by me and a Featured article) and see how to reference sources. I have also posted some hints on the issue in User talk:NeuroJoe/BI481 Spring 2011 along many other comments that may serve you.


 * Additionally I have to say that although I have only made a quick reading of the article I do not see why Alzheimer's or Parkinson's disease are treated so extensively since the article is about excytatory synapses and at no point is the relevance of this for the two disease stated. Similarly occurs with the Excitotoxicity section. Even if excitatory synapses are relevant enough for AD and PD to mention the two disease I doubt that full paragraphs on its treatment or symptoms are suitable in this article...

Summarizing: it seems crucial than the structure and content of this article should be greatly rethought before continuing with it. It might be a good idea if you talked to Mr Burdo about this.

I am sorry if my first comments are quite negative in comparison to those made to some of your companions, however I hope they serve to make you clear that article at the moment has important problems. You are still in time of fixing them. Bests.--Garrondo (talk) 15:03, 25 March 2011 (UTC)


 * After a quick scan of the article I would agree. There should be more balance in the article, for instance we've discussed at length in the class many normal physiological roles of ACh at the motor end plate, glutamate during LTP and LTD, etc. It's ok to include a disease or pathophysiology section but it needs to be balanced since the topic isn't specifically on a disease process. NeuroJoe (talk) 17:27, 25 March 2011 (UTC)
 * Also, NO COPYRIGHTED IMAGES WITHOUT PERMISSION! NeuroJoe (talk) 17:27, 25 March 2011 (UTC)
 * The best image for this article would probably be Template:Synapse map, because it is schematic and has clickable labels. It can be added to the article by putting  into the text. Looie496 (talk) 17:38, 25 March 2011 (UTC)

I have posted general comments at User talk:NeuroJoe/BI481 Spring 2011: take a look to them since they might be of use. For example: in see also section there should not be articles that have already appeared and linked in the article: Policy is that when a link already appears in the article it should not appear also in the see also section. In this sense "see also" is the place for connected links not mentioned in text. Similarly there is no point in having "red links" in see also section, since the intention of the section its to point to other "existing articles". (I have fixed this one).--Garrondo (talk) 12:38, 28 March 2011 (UTC)

Taken from article for further evolution
Per comments above I have moved the whole section on disease to this talk page, since at this point it makes no sense in article: If evolved making clear importance of excitatory synapses for these diseases it could be readded to the article. --Garrondo (talk) 13:02, 28 March 2011 (UTC)


 * I think the material on excitotoxicity does belong in this article. For the rest of it, I don't see why it was there. Looie496 (talk) 23:38, 28 March 2011 (UTC)

Material is:


 * Excitatory synapses have a fundamental role in information processing within the brain and throughout the peripheral nervous system. Usually situated on dendritic spines, or neuronal membrane protrusions on which glutamate receptors and postsynaptic density components are concentrated, excitatory synapses aid in the electrical transmission of neuronal signals.   The physical morphology of synapses is crucial in understanding their function, and it is well documented that the inappropriate loss of synaptic stability leads to the disruption of neuronal circuits and the resulting neurological diseases.  Although there are innumerable different causes for different neurodegenerative illnesses, such as genetic dispositions or mutations, the normal aging process, parasitic and viral causes, or drug use, many can be traced back to dysfunctional signaling between the neurons themselves, often at the synapse.

Excitotoxicity

 * Main Article: Excitotoxicity

Pathophysiology

 * Since glutamate is the most common excitatory neurotransmitter involved in synaptic neuronal transmission, it follows that disruptions in the normal functioning of these pathways can have severe detrimental effects on the nervous system. A major source of cellular stress is related to glutaminergic overstimulation of a postsynaptic neuron via excessive activation of glutamate receptors (i.e., NMDA and AMPA), a process known as excitotoxicity, which was first discovered accidently by D. R. Lucas and J. P. Newhouse in 1957 during experimentation on sodium-fed lab mice.


 * Under normal conditions, extracellular glutamate levels are held under strict control by surrounding neuronal and glial cell membrane transporters, rising to a concentration of about 1 mM and quickly falling to resting levels. However, when glutamate molecules in the synaptic cleft cannot be degraded or reused, the neuron becomes significantly overstimulated, leading to a neuronal cell death pathway known as apoptosis.  Apoptosis occurs primarily via the increased intracellular concentrations of calcium ions, which flow into the cytosol through the activated glutamate receptors and lead to the activation of phospholipases, endonucleases, proteases, and thus the apoptotic cascade.

Treatment

 * Excitotoxic mechanisms are often involved in other forms of neuronal damage, including hypoglycemia, trauma, stroke, seizures, and many neurodegenerative diseases, and thus have important implications in disease treatment. Recent studies have been performed that incorporate glutamate receptor antagonists and excitotoxic cascade disruptors in order to decrease stimulation of postsynaptic neurons, although these treatments are still undergoing active research.

Alzheimer’s Disease

 * Main Article: Alzheimer’s Disease

Pathophysiology

 * Alzheimer’s Diesease (AD) is the most common form of neurodegenerative dementia, or loss of brain function, and was first described by German psychiatrist and neuropathologist Alois Alzheimer in 1907. 9.	 Diagnosis of the disease often stems from clinical observation as well as analysis of family history and other risk factors, and often includes symptoms such as memory impairment and problems with language, decision-making, judgment, and personality.


 * The primary neurological phenomena that lead to the above symptoms are often related to signaling at excitatory synapses, and stem from the presence of amyloid plaques and neurofibrillary tangles, as well as neuronal cell death and synaptic pruning. Amyloid plaques, found throughout the central nervous system in AD patients, are extracellular deposits of the β-amyloid protein that interfere with normal neuronal synaptic signaling due to the production of free radicals and the effectuation of apoptotic mechanisms.     Neurofibrillary tangles, known as a primary marker for AD, are formed by the hyperphosphorylation of the tau protein, associated with cytoskeletal microtubules, causing it to aggregate and clump into an insoluble form.  The tau protein is essential for the proper growth and development of healthy neurons, and thus its inactivity can lead to cell death.

Treatment

 * Although there is at present no cure for Alzheimer’s, several therapies have been developed that slow the progression of the disease, manage behavioral problems, and improve the overall state of living of the patient.


 * The principle drug treatments on the market deal with antagonizing glutamate (NMDA) receptors at neuronal synapses, such as memantine, and inhibiting the activity of acetylcholinesterase, such as donepezil, rivastigmine, and galantamine. A number of labs are currently focusing on prevention of amyloid plaques and other AD symptoms, however, often via the use of experimental vaccines, although this are of research is yet in its infancy.

Parkinson’s Disease

 * Main Article: Parkinson's Disease

Pathophysiology

 * Parkinson’s Disease (PD) is a neurodegenerative disease resulting from the apoptosis of dopaminergic neurons in the central nervous system, especially the substantia nigra, as well as heightened response to the excitatory neurotransmitter, glutamate (i.e., excitotoxicity). While the most obvious symptoms are related to motor skills, prolonged progression of the disease can lead to cognitive and behavioral problems as well as dementia.  Although the mechanism of apoptosis in the brain is not entirely clear, speculation associates cell death with abnormal accumulation of ubiquitinated proteins in cell occlusions known as Lewy bodies, as well as hyperstimulation of neuronal NMDA receptors with excessive glutamate neurotransmitter via the aforementioned pathway.

Treatment

 * Like Alzheimer’s, Parkinson’s Disease lacks a cure. Therefore, in addition to lifestyle changes and surgery, the goal of pharmaceutical drugs used in the treatment of PD patients is to control symptoms and limit, when possible, the progression of the disease.  Levodopa (L-DOPA), the most widely used treatment of PD, is converted to dopamine in the body and helps to relieve the effect of decreased dopaminergic neurons in the central nervous system.  Other dopamine agonists have been administered to patients in an effort to mimic dopamine’s affect at excitatory synapses, binding its receptors and causing the desired postsynaptic response.

Peer Review
Overall, you guys have done a good job explaining the primary functions of excitatory synapses and outlining the steps involved in transmission, but I think that there is room for improvement. I think some minor rearranging of the introductory section could make it more cohesive and give it a better flow. (Even just removing some of the spaces between individual sentence, especially the last two, would help strengthen the connections between them). As another minor point - make sure that the capitalization in your titles conforms to Wikipedia standards (no capitalization within the titles). In the chemical v. electrical synapse sections, you do a good job explaining what an electrical synapse is but do not explain what the function of a chemical synapse is. This was addressed in the opening paragraph but since you have a separate section for the two different synapses, I think you should further explain the distinction here. It might be beneficial to add a section describing how excitatory synapses were first discovered and the various studies that have been done relating to them. As for the section on disease that has been removed, perhaps you could add in a section such as "clinical implications" and there discuss excitotoxicity and briefly address the diseases in which dysfunction of excitatory synapses plays a primary role (without giving them separate sections or going into too much irrelevant detail). Great job so far, hope these suggestions are helpful. Kamilaosypiuk (talk) 02:08, 7 April 2011 (UTC)

I think this article had all the necessary information in a nutshell. However, I think it would be better to have more details on all of subheadings. For instance, more of biochemistry and mechanisms involved in the chemical synaptic transmission would better elucidate the article overall. You can mention where electrical synapses are mainly found within our nervous system (to add to the chemical vs electrical synapses heading). You also mentioned that the first electrical synapse was discovered in crayfish and maybe you can add a research section describing the finding and discuss current ongoing related research. Also, I think you can add more links to your article to better accommodate the viewer. (e.g. NMDA receptor, AMPA receptor, G-protein coupled receptor, hypothalmus, etc.) Thanks, Young B. (talk) 7:00 7 April 2011 (UTC)

Peer Review #2
Overall you've done a great job so far! Now for the critical comments. Firstly, I think you could add an "anatomical location section". This section could describe (statistics would be useful) what bodily areas (brain regions, organs etc.) excitatory synapses are more likely to be found. You might also want to consider doing this for individual excitotoxic neurotransmitters like serotonergic, dopaminergic "areas" etc. Another paragraph that you could add is a disease section, whereby you give a brief list of diseases involving the excitotoxic synapse. Be careful not to focus too much on the disease itself here, and instead center in on the excitotoxic synaptic mechanism(s). I would also recommend including a schematic diagram and/or mechanism picture for a general excitotoxic neurotransmitter like glutamate. Furthermore, when I read the introduction section, it seemed a little bit too detailed and long. I would shorten it to about four or five sentences. Phil J. (talk) 06:01, 7 April 2011 (UTC)

Peer Review #3
So far this article is looking good, while there are a few areas of improvement. We may be able to learn from eachother's articles/topics, mine being "summation", which could potentially be a brief section of your page. I think your introduction could also be more concise, especially if you can consolidate it into a single paragraph or two. Also, in the second paragraph of your introduction you mention EPSPs between electrical synapses, which I found a bit confusing. I take it that EPSPs and IPSPs are an intrinsic modulatory characteristic of chemical synapses and not electrical ones, but I could be misinformed. Another potential addition would be a small section on excitotoxicity, instead of going into length with specific diseases. I also like how you guys brought receptors into the picture when describing neurotransmitters - maybe you can go further into depth about them, since they are ultimately what's exciting the neurons. A few more sources wouldn't hurt either. (Amichael22 (talk) 23:33, 7 April 2011 (UTC))

Peer Review #4
In general I thought the article is informative. I think the last sentences in the introduction could use some explanation on how it is related to excitatory synapses. The Chemical v. Electrical synapses section could be broken down into all of the types of synapses, such as gap junctions, ligand-gated ion channels, and metabotropic receptors. If possible some detail could be added to serotonin and histamine. I also agree with the comment that a section about summation would be nice. In addition, I suggest adding a section about excitotoxicity, current research and drugs and their effect on the synapses. Pictures would be nice also.(canesir (talk) 21:11, 7 April 2011 (UTC))

Peer Review #5
Well done guys, you have greatly improved upon this article. However, I have some suggestions that could make it even better. The article could be greatly improved by adding some images, specifically of the structure of a synapse. An image of a synapse can probably be found in the Wiki commons so it will be painless to add to the article. The Responses of the Postsynaptic Neuron section is very dense with a lot of scientific terms and concepts that will be very difficult for lay people to understand. Although many of these terms are completely necessary, it may be a good idea to add a sentence that summarizes each concept to make it accessible to multiple demographics. Overall you have done a good job in providing a comprehensive view of the excitatory synapses. Keep it up!

Bsnawder (talk) 03:33, 8 April 2011 (UTC)

Peer Review #6
Excitatory synapses are a complex topic, and I really enjoyed your recent edits to the page. However, I believe some improvements could be made in your discussion of Excitotoxicity. While there is clear emphasis on glutamate as the prime excitatory neurotransmitter, I recommend a brief mention of the Glutamate-Glutamine cycle, and its correlation with excitotoxicity. In addition, NMDA and AMPA receptors play a key role in postsynaptic stimulation in excitatory synapses. Their involvement in transmission and excitotoxicity should be mentioned as well. Although the article considers hypoglycemia, trauma, and seizures are possible mechanisms, its important to explain the consequences on the cellular level: such as the buildup of NO and reactive oxidative species that ultimately lead to cell death. I also agree with the previous peer review in that a few pictures would improve the article. Good work guys.

Robinsao (talk) 08:08, 8 April 2011 (UTC)

Peer Review #7
Interesting topic which takes some careful explaining which I feel you guys did very well with. The information in your recent edit proceeds very organized and contains relevant links. I like how your broke apart paragraphs as well. I am uncertain whether or not it is most relevant to include excitatory neurotransmitters where you did, somewhere else in the article, or whether it might be better to abbreviate this section and link out, but this is something to think about. I do like how your broke down the types of synapses but agreeing with the other posters pictures would be very helpful. I am not sure how necessary it is to mention excitatory neurotransmitters or if it wouldn't be better to link out to another article on this and also abbreviate this section. Additionally the "other neurodegenerative diseases" section seems out of place as this is not an article which should be spending a lot of time describing neurodegenerative diseases. Also I would recommend integrating the see also section into their relevant sections. Great work otherwise, lots of good information.Reedyziw (talk) 03:55, 9 April 2011 (UTC)

Some additional suggestions
The article has made great improvement recently. I have some comments. The term presynaptic transmission doesn't make sense, and I'm not aware of its use in the literature. There should be some mention that catecholamine and serotonin are usually thought of as neuromodulators rather than excitatory neurotransmitters but in some instances like in the Aplysia nervous system, dopamine can act as an excitatory transmitter as well (this is the only instance I can think of off-hand but I am sure that there are many other instances in the animal kingdom). I also recommend that the page be reorganized. Here is a potential organization of the main sections.
 * Intro-
 * History/Discovery
 * Excitatory Synaptic Transmission
 * Postsynaptic response
 * Excitatory Neurotransmitters
 * Chemical v. Electrical Synapse
 * Disease

There are also many nomenclature issues that need to be addressed. For instance, postsynaptic density is a component of the cytoskeleton and not the synaptic membrane. I don't think there is a consensus as to whether the receptors themselves are considered a constituent of the PSD, but it is my understanding that the PSD binds to the receptors. So, they are two entities. Hope this helps. Studentne (talk) 04:35, 12 April 2011 (UTC)

End of Boston College BI481 Project
Hi Sam, Rod and Gabriella, nice job with the article in general. It's in much better shape than before obviously. Just a few issues:
 * It's not appropriate to use a retail web site as a reference. http://www.nutramed.com/brain/neurotransmitters_serotonin.htm sells nutritional supplements to "enhance" brain function (whatever that means), so they are not a reliable, unbiased source of background information.
 * There are several comments from class peer review that weren't implemented in your finished product, which is fine, but you need to respond back to the authors as to why you did not implement the suggestions.
 * A few of the references, while appropriate, need more of a description so your reader can see where they came from at a glance.
 * From the Disease/Treatment section: "Excitotoxic mechanisms are often involved in other forms of neuronal damage, including hypoglycemia, trauma, stroke, seizures, and many neurodegenerative diseases," Those are conditions, they are not forms of neuronal damage. NeuroJoe (talk) 22:22, 5 May 2011 (UTC)

Review
I have compared this version of the page,, from before the start of the project, with this version, , after.

Scale from 1 to 5 1 = most negative 5 = most positive

1. Is the prose clear and concise? 5

2. Does the article comply with the manual of style guidelines for lead sections, layout, words to watch, and list incorporation? 2: Problems: The first mention of the article subject in the lead needs to be bold, not italic. The paragraph text of the sections should not be indented. Some of the inline citations are placed incorrectly (after spaces, or before punctuation), and look at the first sentence in the paragraph about Alzheimer's disease. Also some words (such as the names of the catecholamines) are improperly capitalized.

3. Is the article properly and adequately referenced? 5

4. Are in-line citations provided in accordance with Scientific citation guidelines? 5

5. Does the article address the main aspects of the topic? 5, but see next point.

6. Does the article stay focused on the topic without going into unnecessary detail? 2: The page has material in it that I don't think really belongs here. It's debatable whether Alzheimer's and Parkinson's diseases really have anything to do with excessive excitatory transmission, and most modern research would say that they really do not. And look at what you wrote about some of the neurotransmitters: if they open K+ channels, wouldn't they be inhibitory instead of excitatory? Several of them actually are!

7. Does the article represent viewpoints fairly and without bias? 4: I think a case could be made that some of the section on diseases violates WP:UNDUE by suggesting excitotoxic mechanisms that are not the majority view in the literature.

8. Is the article illustrated by images that are relevant and are tagged with their proper status? 5: I especially like the way high quality images have been added to the page.

Overall, I think the page has been expanded considerably and looks much better than it used to. I think that the major weakness (per item 6) is that there is material that was added indiscriminately and should not be here. --Tryptofish (talk) 20:04, 14 May 2011 (UTC)