A von Economo neuron, also known as a spindle neuron, is a unique cell with several interesting characteristics:
1) It has a long axon and on the opposite side of the cell body has only one long dendrite, resembling a spindle and hence the nickname.
2) It is to be found only in humans, apes, elephants, dolphins, whales, and a few other animals known for their intricate social structure.
3) In humans, they exist only in the frontal part of the brain.
4) It is thought to be important for social awareness.
In all fairness, these cells should be called Betz cells, or at least Ramón y Cajal cells because these neuroanatomists mentioned their existence in 1881 and 1904, respectively. But Betz already has his own neurons, and Ramón y Cajal, well… his fame is established already. But von Economo “made a more complete description of their morphology and mapped their specific locations in human cortex” (Allman et al., 2011)
So what do we know about von Economo? Quite a lot, thanks to Triarhou, an excellent biographer. Constantin von Economo (1876–1931) was born in Brăila, Romania to a wealthy family of Greek descent. Shorty after his birth, the family moved from Romania to Austria where the father acquired a “von” in front of his name by way of elevation to the rank of baron.
Von Economo went to medical school in Vienna, traveled a lot across the globe, graduated, spent some more time here and there learning psychiatry, physiology, neurology and such with some Big Names, then returned to Vienna where he followed the classic academic path (for his time). He was a prolific writer, having published at least 139 scientific works in a relatively short time.
Besides the spindle neurons, he is also known for publishing an awesome brain atlas in 1925 (with Georg Koskinas) and for investigating in detail a mysterious and weird disease, encephalitis lethargica (the ‘von Economo disease’). This disease has unknown causes to the day, partly because it is very difficult to study, having virtually disappeared form the face of the Earth after a furious epidemic in 1926. But about that enigma some other time.
For now, enjoy von Economo’s drawings.
Notes: 1) One last thing. Although according to Springer’s website the copyright for the von Economo paper I’m citing should have expired, Springer still charges a lot of money to obtain it (if you don’t have an institutional license like some of us, the fortunates, that is). I have attempted to contact Springer about it with no luck. Anyway, if you want it, email me at firstname.lastname@example.org. It’s been more than 70 years since the death of the author, so it should be public domain.
2) I have no idea why people reference the Ramón y Cajal’s Textura del Sistema Nervioso del Hombre y de los Vertebrados as published in 1889. I got it from Google Books and it says 1904 on it.
By Neuronicus, 25 September 2016
Memory processes like formation, maintenance and consolidation have been the subjects of extensive research and, as a result, we know quite a bit about them. And just when we thought that we are getting a pretty clear picture of the memory tableau and all that is left is a little bit of dusting around the edges and getting rid of the pink elephant in the middle of the room, here comes a new player that muddies the waters again.
DNA methylation. The attaching of a methyl group (CH3) to the DNA’s cytosine by a DNA methyltransferase (Dnmt) was considered until very recently a process reserved for the immature cells in helping them meet their final fate. In other words, DNA methylation plays a role in cell differentiation by suppressing gene expression. It has other roles in X-chromosome inactivation and cancer, but it was not suspected to play a role in memory until this decade.
Oliveira (2016) gives us a nice review of the role(s) of DNA methylation in memory formation and maintenance. First, we encounter the pharmacological studies that found that injecting Dnmt inhibitors in various parts of the brain in various species disrupted memory formation or maintenance. Next, we see the genetic studies, where mice Dnmt knock-downs and knock-outs also show impaired memory formation and maintenance. Finally, knowing which genes’ transcription is essential for memory, the researcher takes us through several papers that examine the DNA de novo methylation and demethylation of these genes in response to learning events and its role in alternative splicing.
Based on these here available data, the author proposes that activity induced DNA methylation serves two roles in memory: to “on the one hand, generate a primed and more permissive epigenome state that could facilitate future transcriptional responses and on the other hand, directly regulate the expression of genes that set the strength of the neuronal network connectivity, this way altering the probability of reactivation of the same network” (p. 590).
Here you go; another morsel of actual science brought to your fingertips by yours truly.
Reference: Oliveira AM (Oct 2016, Epub 15 Sep 2016). DNA methylation: a permissive mark in memory formation and maintenance. Learning & Memory, 23(10): 587-593. PMID: 27634149, DOI: 10.1101/lm.042739.116. ARTICLE
By Neuronicus, 22 September 2016
Reference: von Bonin, G. (1950). Essay on the cerebral cortex. Ed. Charles C. Thomas, Springfield. ISBN 10: 0398044252, ISBN 13: 9780398044251
Image credit: geralt.The whole image: Public Domain
By Neuronicus, 15 September 2016
Wayne State University. Ever heard of it? Probably not. How about Zhuo-Hua Pan? No? No bell ringing? Let’s try a different approach: ever heard of Stanford University? Why, yes, it’s one of the most prestigious and famous universities in the world. And now the last question: do you know who Karl Deisseroth is? If you’re not a neuroscientist, probably not. But if you are, then you would know him as the father of optogenetics.
Optogenetics is the newest tool in the biology kit that allows you to control the way a cell behaves by shining a light on it (that’s the opto part). Prior to that, the cell in question must be made to express a protein that is sensitive to light (i.e. rhodopsin) either by injecting a virus or breeding genetically modified animals that express that protein (that’s the genetics part).
If you’re watching the Nobel Prizes for Medicine, then you would also be familiar with Deisseroth’s name as he may be awarded the Nobel soon for inventing optogenetics. Only that, strictly speaking, he did not. Or, to be fair and precise at the same time, he did, but he was not the first one. Dr. Pan from Wayne State University was. And he got scooped.
The story is at length imparted to us by Anna Vlasits in STAT and republished in Scientific American. In short, Dr. Pan, an obscure name in an obscure university from an ill-famed city (Detroit), does research for years in an unglamorous field of retina and blindness. He figured, quite reasonably, that restoring the proteins which sense light in the human eye (i.e. photoreceptor proteins) could restore vision in the congenitally blind. The problem is that human photoreceptor proteins are very complicated and efforts to introduce them into retinas of blind people have proven unsuccessful. But, in 2003, a paper was published showing how an algae protein that senses light, called channelrhodopsin (ChR), can be expressed into mammalian cells without loss of function.
So, in 2004, Pan got a colleague from Salus University (if Wayne State University is a medium-sized research university, then Salus is a really tiny, tiny little place) to engineer a ChR into a virus which Pan then injected in rodent retinal neurons, in vivo. After 3-4 weeks he obtained the expression of the protein and the expression was stable for at least 1 year, showing that the virus works nicely. Then his group did a bunch of electrophysiological recordings (whole cell patch-clamp and voltage clamp) to see if shining light on those neurons makes them fire. It did. Then, they wanted to see if ChR is for sure responsible for this firing and not some other proteins so they increased the intensity of the blue light that their ChR is known to sense and observed that the cell responded with increased firing. Now that they saw the ChR works in normal rodents, next they expressed the ChR by virally infecting mice who were congenitally blind and repeated their experiments. The electrophysiological experiments showed that it worked. But you see with your brain, not with your retina, so the researchers looked to see if these cells that express ChR project from the retina to the brain and they found their axons in lateral geniculate and superior colliculus, two major brain areas important for vision. Then, they recorded from these areas and the brain responded when blue light, but not yellow or other colors, was shone on the retina. The brain of congenitally blind mice without ChR does not respond regardless of the type of light shone on their retinas. But does that mean the mouse was able to see? That remains to be seen (har har) in future experiments. But the Pan group did demonstrate – without question or doubt – that they can control neurons by light.
All in all, a groundbreaking paper. So the Pan group was not off the mark when they submitted it to Nature on November 25, 2004. As Anna Vlasits reports in the Exclusive, Nature told Pan to submit to a more specialized journal, like Nature Neuroscience, which then rejected it. Pan submitted then to the Journal of Neuroscience, which also rejected it. He submitted it then to Neuron on November 29, 2005, which finally accepted it. Got published on April 6, 2006. Deisseroth’s paper was submitted to Nature Neuroscience on May 12, 2005, accepted on July, and published on August 14, 2005… His group infected rat hippocampal neurons cultured in a Petri dish with a virus carrying the ChR and then they did some electrophysiological recordings on those neurons while shining lights of different wavelengths on them, showing that these cells can be controlled by light.
There’s more on the saga with patent filings and a conference where Pan showed the ChR data in May 2005 and so on, you can read all about it in Scientific American. The magazine is just hinting to what I will say outright, loud and clear: Pan didn’t get published because of his and his institution’s lack of fame. Deisseroth did because of the opposite. That’s all. This is not about squabbles about whose work is more elegant, who presented his work as a scientific discovery or a technical report or whose title is more catchy, whose language is more boisterous or native English-speaker or luck or anything like that. It is about bias and, why not?, let’s call a spade a spade, discrimination. Nature and Journal of Neuroscience are not caught doing this for the first time. Not by a long shot. The problem is that they are still doing it, that is: discriminating against scientific work presented to them based on the name of the authors and their institutions.
Personally, so I don’t get comments along the lines of the fox and the grapes, I have worked at both high profile and low profile institutions. And I have seen the difference not in the work, but in the reception.
That’s my piece for today.
1) Bi A, Cui J, Ma YP, Olshevskaya E, Pu M, Dizhoor AM, & Pan ZH (6 April 2006). Ectopic expression of a microbial-type rhodopsin restores visual responses in mice with photoreceptor degeneration. Neuron, 50(1): 23-33. PMID: 16600853. PMCID: PMC1459045. DOI: 10.1016/j.neuron.2006.02.026. ARTICLE | FREE FULLTEXT PDF
2) Boyden ES, Zhang F, Bamberg E, Nagel G, & Deisseroth K. (Sep 2005, Epub 2005 Aug 14). Millisecond-timescale, genetically targeted optical control of neural activity. Nature Neuroscience, 8(9):1263-1268. PMID: 16116447. DOI: 10.1038/nn1525. doi:10.1038/nn1525. ARTICLE
By Neuronicus, 11 September 2016