Wikipedia talk:WikiProject Neuroscience

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See discussion importing content from database into WP[edit]

Here: Wikipedia_talk:WikiProject_Molecular_and_Cell_Biology#Transporter_classification_database Jytdog (talk) 22:09, 24 April 2016 (UTC)

There continue to be issues that are directly related to neuroscience there, as well as at Talk:Voltage-gated ion channel. --Tryptofish (talk) 22:17, 4 May 2016 (UTC)

deep sleep -- a suggestion[edit]

Will someone knowledgeable please look at Talk:Neuroscience of sleep, new section "deep sleep". An IP has made a suggestion there and I have replied; neither of us is qualified to act on it. Thank you, --Hordaland (talk) 15:25, 25 April 2016 (UTC)

Thanks for asking here. I made a reply there. --Tryptofish (talk) 20:28, 25 April 2016 (UTC)

Issues in the Cerebellum article[edit]

The Cerebellum article is a candidate for publication in Wikiversity Journal of Medicine (Wikiversity draft located here). When published, the snapshot in Wikiversity will be easier for external sources to cite, and it will give clear credit to those who have contributed the most to creating the article. However, first it needs some amendment in regard to the issues found in by the peer reviewer, copied to here:

The article is very informational and is written in an encyclopedic voice. It is written at a scholarly level while still maintaining enough readability for lay readers. Though, I suggest a few changes (highlighted in the attached pdf).

1. While the article provides a comprehensive overview of the cerebellum in terms of its structure and functions, certain aspects of its anatomy are still lacking:
- Information on blood supply should be added (superior cerebellar artery, anterior inferior cerebellar artery, and posterior inferior cerebellar artery), perhaps with illustrations.
- Its connections to the brainstem (the three cerebellar peduncles) and tracks (e.g., cerebellothalamic tract) should be mentioned.

2. Information on cerebellar anomalies should also be added to section 'Clinical significance', e.g., Arnold-Chiari malformation, Dandy-Walker syndrome, etc.

Other comments:
1. I notice some missing citations at several locations:
- Page 1, 'Most of them derive from....., Purkinje cell receives two dramatically...., The basic concept of Marr-Albus.....
- Page 5, last paragraph of section 1.2.1 Purkinje cell, The most popular concept of their function....
- Page 7, section 2 Function, last paragraph, Kenji Doya has argued......
- Page 9, second paragraph of section 2.3 Theories and computational methods, Perhaps the earliest "performance" theory...

2. Page 3, Figure: Microcircuitry of the cerebellum, abbreviation of CFC is lacking.
3. Page 7, section 1.2.5 Deep nuclei, use the word 'supply' instead of 'innervate'.

Also, User:Tony1 asked what "its" refers to for the sentence "This complex neural organization gives rise to a massive signal-processing capability, but almost all of its output passes through a set of small deep cerebellar nuclei lying in the interior of the cerebellum."

As this is among Wikipedia's featured articles, I think it is important to address these matters. Also, please give me a note if you think you think you've made substantial contributions to this article to have your name among the authors in the Wikiversity article. In that case, your real name should be used rather than your username.

Mikael Häggström (talk) 14:52, 9 June 2016 (UTC)

These issues have now been amended. Mikael Häggström (talk) 18:12, 28 June 2016 (UTC)

Human neuroepigenetic (class I histone deacetylase) PET imaging in vivo[edit]

A recently published study used a radiotracer called [11C] Martinostat to accomplish this.[1] I figured I'd post this here in the event anyone is interested in reading the paper or creating an article on the compound (someone created it today). Seems pretty notable considering that this can be used to validate some of the key epigenetic mechanisms from animal models of the molecular neurobiology of addiction in living humans. Seppi333 (Insert ) 00:52, 12 August 2016 (UTC)


  1. ^ Wey HY, Gilbert TM, Zürcher NR, She A, Bhanot A, Taillon BD, Schroeder FA, Wang C, Haggarty SJ, Hooker JM (10 August 2016). "Insights into neuroepigenetics through human histone deacetylase PET imaging". Science Translational Medicine. 8 (351): 351ra106. doi:10.1126/scitranslmed.aaf7551. PMID 27510902. Retrieved 12 August 2016. Lay summaryEpigenetic Activity Imaged in Human Brain for First Time (11 August 2016). In neurological disorders, HDACs change expression in regions throughout the brain, but their dynamic contribution to human disease development over time is unknown. Wey et al. therefore developed and applied an HDAC imaging probe, called Martinostat, to visualize HDAC expression in the living brain. Martinostat was previously tested in rodents and nonhuman primates, and here, it is used for the first time in humans. 

Discussion about notability of a BLP[edit]

More views would be welcome at Wikipedia talk:Notability (academics)#Asking for some other opinions. Thanks. --Tryptofish (talk) 21:57, 15 August 2016 (UTC)

BioRxiv support in citations[edit]

This project's feedback would be appreciated in this discussion, as this could greatly (and positively) affect biological citations! Headbomb {talk / contribs / physics / books} 21:54, 7 September 2016 (UTC)

Dopamine biosynthesis from phenylalanine via meta-tyramine[edit]

Biosynthesis pathway for trace amines and catecholamines in the human brain[1][2][3]
The image above contains clickable links
This diagram appears in these 21 articles as of 22:03, 7 October 2016 (UTC).

Does anyone know of any reliable sources for citing the phenylalaninemeta-tyrosinemeta-tyramine metabolic pathway covered in the Dopamine#Biochemistry section? Meta-tyramine is clearly an endogenous human biomolecule based upon the fact that it's detectable in human biofluids [1] (urine+plasma). I'm just looking for a ref that covers its biosynthesis in humans. Also, if anyone knows of a review article or textbook that covers the enzymatic metabolism of phenylethylamine into para-tyramine in humans, I'd be interested in that as well; I'd add that pathway to the {{Catecholamine and trace amine biosynthesis}} diagram if it's a notable contributor to human p-tyramine biosynthesis. Seppi333 (Insert ) 16:16, 3 October 2016 (UTC)

I've looked into it, and I am very skeptical that it is true. It's chemically plausible, but I think that it is very unlikely to occur biochemically. I've gone through several textbooks that include lots of obscure biochemical pathways, and none of them says anything about it. Furthermore, this source: [2], indicates that meta-tyramine interferes with dopamine biosynthesis in vivo, which would seem to indicate that it is not a precursor to any significant degree. Absent an affirmative source, I'd say it should not be reported on Wikipedia. --Tryptofish (talk) 21:00, 3 October 2016 (UTC)
Dopamine synthesis from p-tyramine and m-tyramine in the human brain by CYP2D6 is covered in this review.[3] Seppi333 (Insert ) 02:48, October 4, 2016 (UTC)
OK, that source does seem sufficient to justify saying that it can occur via that pathway. However, that brings us to the question of whether this is a significant contributor to dopamine biosynthesis, or something that only contributes trace amounts. According to the abstract of the source, the 2D6 isoform appears to be expressed only under pathological conditions. And the text that you quote here indicates that 2D6 has a Km value in the ballpark of 0.1 mM. That's a very high concentration of meta-tyramine needed for significant enzymatic activity, and it sounds like no other isoform has a lower Km than 2D6. I'm guessing that a full reading of the source (I don't have access to the full text), and maybe some papers that it cites, would indicate that this pathway is negligible under normal conditions, but becomes measurable under pathological conditions like Parkinson's disease, where the normal biosynthetic pathway is suppressed. --Tryptofish (talk) 19:47, 4 October 2016 (UTC)
@Tryptofish: Hmm. I figured that, based upon the wording of the brain CYP2D review (temporarily available here), it was notable enough to add as an alternative pathway. In case you'd like to read the primary source that the review[3] cited when covering the substrate affinity (Km) of tyramine for human and rat CYP2D enzymes in the reference quote, here's a link to it. Trace amines (most of which function solely as monoamine neuromodulators as opposed to neurotransmitters), including tyramine, are produced at roughly the same rate as normal monoamine neurotransmitters but are metabolized much more extensively, hence the relatively low concentrations in cerebrospinal fluid + peripheral blood plasma and on the basis of micrograms/gram of brain tissue (in rats/mice) relative to "classical" monoamines.[note 1] However, the concentration of trace amines in blood plasma appears to markedly increase over short time periods as a result of stimulus-induced augmentation of their rate of biosynthesis.[note 2] If you want me to upload any other sources for you, just link me to the PMID and I'll temporarily upload the full version + provide a link for you to view/download it.
FWIW, the reasons that I figured this pathway was notable other than what was mentioned in that review are: this in vitro paper - PMID 21679153 - which suggests that CYP2D6 plays a dominant role in tyramine metabolism (w/ FMO3 and MAO-A/MAO-B contributing more to its metabolism in individuals w/ loss-of-function mutations in the CYP2D6 enzyme); and this primary source - PMID 20832343 - about peripheral dopamine biosynthesis/excretion in AADC-deficient individuals, which stated "CYP2D6-mediated conversion of tyramine into dopamine might be an interesting target for the development of new therapeutic strategies in AADC-deficiency."
Anyway, if you believe that it's not worth covering "L-tyrosine → p-tyramine → dopamine" and "L-phenylalanine → meta-tyrosine → meta-tyramine → dopamine" as alternative pathways for human dopamine biosynthesis in Dopamine#Biochemistry and in the biosynthesis diagram in this section, I have no problem with removing those pathways – just let me know. On a related note, assuming you think it's appropriate to cover dopamine biosynthesis from meta-tyramine in the dopamine article, should I remove the "L-phenylalanine → meta-tyrosine → meta-tyramine → dopamine" pathway from the Dopamine#Biochemistry section until the first 2 transformations are referenced, or should I leave that in for now? "L-phenylalanine → meta-tyrosine → meta-tyramine" isn't cited at the moment. Seppi333 (Insert ) 21:11, 7 October 2016 (UTC)
Thanks for this information. I see now that you are also asking about the para-tyramine pathway. When I wrote my previous answers, I was only thinking about the meta-tyramine pathway, so that may be two different issues. I've downloaded both those papers, so that I can read them in full. I'll need a few days to work through all this new information, but I'll reply again when I have taken it all in. --Tryptofish (talk) 22:33, 7 October 2016 (UTC)
Nevermind my second question. I just noticed that BRENDA's tyrosine 3-hydroxylase entry for homo sapiens lists L-phenylalanine as an enzyme substrate and 3-hydroxyphenylalanine (meta-tyrosine) as the product.[4] BRENDA's AADC entry for homo sapiens lists m-tyrosine as a substrate and m-tyramine as the product.[5] I'm just going to cite these in the dopamine article for now. Seppi333 (Insert ) 23:24, 7 October 2016 (UTC)

@Seppi333: I've finally gotten around to reading these sources carefully – thanks for your patience. Because the figure above is about the human brain, I'm going to focus on the brain, rather than blood or liver, where perhaps things might be different.

After reading carefully, my answer is actually just about the same as it was before! I think the key place to focus on is indeed the Bromek study. It's important to note that they did most of their studies in brain microsomes, rather than in brain tissue in situ. That means that they are preparing their test samples to be enriched in what they are measuring, in comparison to natural brain tissue, and that's helpful in determining whether the pathway can happen. But I want to draw attention to page 177, left column, the paragraph beginning "The physiological and pharmacological significance...", because that's where they (correctly, in my opinion) evaluate how their microsome results might relate to natural brain tissue. They say: Our study shows that the Km value of CYP2D-dependent tyramine hydroxylase is higher (256 μM for CYP2D4 and m-tyramine) than that of tyrosine hydroxylase (55 μM for soluble enzyme and L-tyrosine) (Kuczeński and Mandell, 1972), which suggests greater ability of the latter enzyme (a classic biosynthetic route) to form dopamine in the rat brain (Vmax values could not be compared because of different enzyme preparations and reaction conditions). However, one cannot exclude the possibility that an alternative CYP2D-mediated pathway of dopamine synthesis contributes to the overall concentration of this neurotransmitter in certain areas of the brain, especially under conditions of enzyme induction by nicotine (Mann et al., 2008; Miksys and Tyndale, 2004; Yue et al., 2008) and/or in situations when the classic pathway via tyrosine hydroxylase is deficient (neurodegenerative diseases).

That's very much confirming what I suspected earlier. The conversion of m-tyramine to to dopamine only occurs at m-tyramine concentrations that are very high (and even higher for p-tyramine), whereas the "classic biosynthetic route" utilizing tyrosine hydroxylase has a much "greater ability... to form dopamine in the... brain". In other words, brain dopamine comes pretty much entirely from the classic tyrosine hydroxylase pathway, with only a tiny contribution from tyramine under normal conditions. The tyramine pathway can happen, and does happen, but it only represents a tiny percentage of the dopamine synthesis in the brain under normal conditions. That small percentage is simply something that "one cannot exclude". But they then point out that certain non-normal conditions (nicotine toxicity and neurodegenerative diseases such as Parkinson's) might induce the CYP pathway when the "classic" pathway is inhibited. That's it.

So there are two ways of looking at the content question. One way is to treat the tyramine stuff (both m- and p-) as something that exists and is chemically possible, but is a biologically minor pathway. The other is to leave it out or relegate it to something like a footnote. I don't care which of those approaches you choose. But I would advise against treating it as co-equal with the tyrosine pathway. I hope that helps. --Tryptofish (talk) 20:09, 20 October 2016 (UTC)

@Tryptofish: I tried to note that these were minor pathways in the dopamine article when I covered this there, but to further clarify, I've added the highlighted text in the excerpt below from Dopamine#Biochemistry:

The primary and minor metabolic pathways respectively are:

Primary: L-Phenylalanine → L-Tyrosine → L-DOPA → Dopamine[1][2]
Minor: L-Phenylalanine → L-Tyrosine → p-Tyramine → Dopamine[1][2][3]
Minor: L-Phenylalanine → m-Tyrosinem-Tyramine → Dopamine[3][4][5]
— Dopamine#Biochemistry
Does that address your concerns about the article text? Also, do you think I should mention somewhere in the metabolic pathway diagram (i.e., {{Catecholamine and trace amine biosynthesis}}) that it's a minor pathway or just leave the image as is? Seppi333 (Insert ) 20:32, 20 October 2016 (UTC)
Yes, I think that "primary" and "minor" labeling works very well. Thanks! As for the diagram, I'd be inclined to put the word "(minor)" in parentheses right after "brain CYP2D6", next to the arrow going from p-tyramine to dopamine (ie, "brain CYP2D6 (minor)"). Thanks for all your good work on editing these pages! --Tryptofish (talk) 20:46, 20 October 2016 (UTC)


  1. ^ I'm not really sure if AADC is colocalized within the same intracellular compartments as CYP2D6 or monoamine oxidases in neurons, but if AADC and CYP2D6 are in closer proximity to one another relative to AADC and MAO, the local concentration of tyramine in the vicinity of CYP2D6 would probably be non-trivially greater than the local concentration of tyramine in the vicinity of MAO enzymes.
  2. ^ For example, see the text/references in Phenethylamine#Detection in body fluids. I'm not really sure how phenethylamine's biosynthesis can greatly increase without a similar increase in the rate of dopamine biosynthesis occurring simultaneously (in the brain, PEA is primarily produced from phenylalanine from AADC in DA/NE neurons); however, the refs state that a massive but transient increase in the rate of phenethylamine synthesis occurs as a result of both aerobic exercise and skydiving. Phenethylamine, tyramine, and dopamine are all produced by AADC enzymes, but I have no clue if these stimuli induce a similar effect on tyramine biosynthesis since this wasn't examined in the cited studies in the phenethylamine article. It is worth noting though that aerobic exercise does induce DA release from at least three sets of DA projections that originate in the VTA + substantia nigra (nigrostriatal + mesocortical + mesolimbic pathways). Therefore, I imagine that exercise would also induce an increase in DA biosynthesis in those neurons.



  1. ^ a b c Broadley KJ (March 2010). "The vascular effects of trace amines and amphetamines". Pharmacol. Ther. 125 (3): 363–375. doi:10.1016/j.pharmthera.2009.11.005. PMID 19948186. 
  2. ^ a b c Lindemann L, Hoener MC (May 2005). "A renaissance in trace amines inspired by a novel GPCR family". Trends Pharmacol. Sci. 26 (5): 274–281. doi:10.1016/ PMID 15860375. 
  3. ^ a b c d e Wang X, Li J, Dong G, Yue J (February 2014). "The endogenous substrates of brain CYP2D". Eur. J. Pharmacol. 724: 211–218. doi:10.1016/j.ejphar.2013.12.025. PMID 24374199. The highest level of brain CYP2D activity was found in the substantia nigra (Bromek et al., 2010). The in vitro and in vivo studies have shown the contribution of the alternative CYP2D-mediated dopamine synthesis to the concentration of this neurotransmitter although the classic biosynthetic route to dopamine from tyrosine is active. CYP2D6 protein level is approximately 40% lower in the frontal cortex, cerebellum, and hippocampus in PD patients, even when controlling for CYP2D6 genotype (Mann et al., 2012). ... Tyramine levels are especially high in the basal ganglia and limbic system, which are thought to be related to individual behavior and emotion (Yu et al., 2003c). Studies have demonstrated that dopamine is formed from p-tyramine as well as m-tyramine via tyramine 3-hydroxylation or 4-hydroxylation by rat CYP2D2, 2D4, and 2D18 as well as human CYP2D6. ... Both rat CYP2D and human CYP2D6 have a higher affinity for m-tyramine compared with p-tyramine for the generation of dopamine. Rat CYP2D isoforms (2D2/2D4/2D18) are less efficient than human CYP2D6 for the generation of dopamine from p-tyramine. The Km values of the CYP2D isoforms are as follows: CYP2D6 (87–121 μm) ≈ CYP2D2 ≈ CYP2D18 > CYP2D4 (256 μm) for m-tyramine and CYP2D4 (433 μm) > CYP2D2 ≈ CYP2D6 > CYP2D18 (688 μm) for p-tyramine (Bromek et al., 2010; Thompson et al., 2000). 
  4. ^ a b "EC – Tyrosine 3-monooxygenase (Homo sapiens)". BRENDA. Technische Universität Braunschweig. July 2016. Retrieved 7 October 2016. 
  5. ^ a b "EC – Aromatic-L-amino-acid decarboxylase (Homo sapiens)". BRENDA. Technische Universität Braunschweig. July 2016. Retrieved 7 October 2016. 

Research of different species in the article "Visual cortex"[edit]

I noticed that the article Visual cortex contains information about the visual cortices of different species. The problem is that this article gives the illusion that all brains are structured in the same way.

The aim on the project page says: "This project's approach is to cover the brain from a cross-species, multidisciplinary perspective. This should provide detailed information about the distinct differences between species, and explain some possible evolutionary/ecological reasons for such differences."

How can this be achieved for the Visual cortex article? VeniVidiVicipedia (talk) 10:35, 17 October 2016 (UTC)

WP:BEBOLD. If you have sources for inter-species comparisons, please add a section about it. --Tryptofish (talk) 21:40, 17 October 2016 (UTC)