NEW OLIGODENDROCYTE RESEARCH: But What Is Really Going On In Our Other BRAIN ?

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BUT WHAT  IS REALLY GOING ON IN OUR OTHER BRAIN ? THE REST OF THE STORY –

A noteworthy finding from this study is to show the presence of oligodendrocytes that dominantly ensheath a particular subset of neurons and that evenly ensheath axons from multiple brain regions.

This is a very interesting new study which brings us some valuable information in regard to how our “favorite cells” in the brain, the glial cells (close favorites over the “microglia” which are also definite ‘faves’) engaged those wildly over famous and fashionable “neurons’ in helping the brain do its works

The report tells us There are three kinds of glial cells in the brain: oligodendrocytes, astrocytes and microglia. Oligodendrocytes myelinate neuronal axons to increase conduction velocity of neuronal impulses.” Vaguely and without any conceptual framing, the report tells us “ A Japanese research team at the National Institute for Physiological Sciences ) has found a characteristic feature of oligodendrocytes that selectively myelinate a particular set of neuronal axons.”

Thus the “model” of the brain of which we speak here very often…and without regard to political correctness or the reluctance of researchers to venture into any zone beyond complete boring safety….entails two key pillars of our Page here” The cells of the other brain…including the three varieties (actualy even more complex a classification than that can be mustered of “glial cells” and the importance of neurogenesis in the daily functioning of the brain (and indeed the analogously important and remarkably similar importance of pluripotent progenitors growth and maturation in all other tissues in our bodies.

This study, however, is, for us, another instance of how neuroscience seems to proceed by picking up scattered pieces of jigsaw puzzle but never even discussion the likelihood that a new model of the brain is necessary and potentially valuable to understanding these fragmentary results. And it is an example of why we just can’t stand the manner in which the medical paprazzi unthinkingly post press releases and then the robotic copying of those press releases by various well intentioned “posters’ on Facebooks

As we read on various Facebook re transimissions of this “story< “ The Japanese research group at NIPS used a viral vector to label single oligodendrocytes in the white matter. With multiple viral vector injections, neuronal axons derived from distinct brain region (motor cortex or sensory cortex) and oligodendrocytes in the white matter were simultaneously labeled

BUT we see no more than the following grossly inadequate statement from the press Medical Pararazzi “Surprisingly, the research group found that oligodendrocytes did not just ensheath axons randomly—some oligodendrocytes selectively myelinated axons from a particular brain region”

http://medicalxpress.com/news/2016-10-oligodendrocytes-myelinate-axons-white.html

So not only is there no “model’ of framework to do anything but memorize these isolated results..but for some odd reason the main aspect and discovery of the research is not even mentioned. This sounds like the political news we have to deal with today.

Of course they mention briefly the routine understandings of oligodendrocytes (from about ten or fifteen years ago), presumably now safe enough to mention in a press release. “

So, OK, then? What is the surface story? And the WHAT IS THE REST OF THE STORY that is not even hinted at in the research of the discussion of that research, and, yet, which we know, from any reading of the research research in neuroscience, to be quite true and salient Now, we note, that as we write this post and other posts, we do NOT have our own laboratory and do our own research on these topics… but we do KNOW that these studies raise key questions and key hypotheses as to what is “going on “in their date…that need to be asked.

The actual link to the published research is here:

http://onlinelibrary.wiley.com/doi/10.1002/glia.23076/abstract;jsessionid=220623906AB3C03418FF6B86C042DC27.f01t04

The researchers point out to us one of the true current mysteries of neurogenesis in our brains.”Oligodendrocytes myelinate neuronal axons during development and increase conduction velocity of neuronal impulses in the central nervous system.

“Recent reports have revealed that depolarization of an oligodendrocyte increases conduc- tion velocity of the axons it myelinates It is possible that each oligodendrocyte prefer- entially ensheaths a particular set of neuronal axons and simultaneously increases conduction velocity of the myelinat- ed axons.

This may help to synchronize electrical impulses traveling through different axons. A recent study suggested that oligo- dendrocytes myelinate neuronal axons depending on neuronal activity ”

Neuronal axons extend from multiple brain regions and pass through the white matter; however, whether oligodendrocytes ensheath a particular set of axons or do so randomly within the mammalian brain remains unclear.

That mystery is not mentioned expressly, but we know here that “ Given that new cells are constantly being created, how in the world do they know where to go and what to do once they are released from their ’ not ready for prime time” status and the sequestering in the neurogenic niche.

In contrast to a Schwann cell that myelinates one axon in the peripheral ner-vous system, an oligodendrocyte in the central nervous system (CNS) extends many processes and myelinates multiple axons The number of processes extending from a single oligodendrocyte varies among different CNS regions. For example, the number of myelin internodes formed by a single oligodendrocyte is higher in the corpus callosum than in the spinal cord

“We found that some populations of oligodendrocytes in the corpus callosum predominantly ensheathed axons derived from motor cortex or sensory cortex, while others ensheathed axons from both brain regions, suggesting heterogeneity in preference of myelination toward a particular subtype of neurons.

“A noteworthy finding from this study is to show the presence of oligodendrocytes that dominantly ensheath a particular subset of neurons and that evenly ensheath axons from multiple brain regions.

It is known that oligodendrocytes are involved in motor skill learning . It would be intriguing to examine if changes in oligodendrocyte morphology and preference for motor axons are related to learning motor skills. Some reports have suggested that a single oligodendro- cyte modulates the function of the neuronal axons it myeli- nates (

They quite aptly speculate, ‘If one oligo- dendrocyte myelinates multiple axons that are targeted to the same brain region, it is possible that the regulation of con- duction velocity by oligodendrocytes synchronizes action potentials traveling to the target region. In contrast, if one oligodendrocyte myelinates axons that are derived from differ- ent brain regions with distinct functions, this could result in cross talk between axons from different regions (such as motor axons vs. sensory axons). “

“It is possible that myelination of specific axons is required for learning, as synchronized inputs from presyn- aptic neurons are important for long-term potentiation and long-term depression. It is also interesting to speculate that axons ensheathed by one oligodendrocyte project to identical neuronal dendrites.

But what is actually going on here: We note with interest (remembering that one oligodendrocytes “ serivces” or actually interreacts with many neurons, that MOST of the oligodendrocytes are actgually not constrained by “regions” as to where they might go…Most have an apparently diverse itineracy for their “travels” once they leave the neurogenic niche.…They tell us.”We found majority (75%) of oligodendrocytes simulta- neously myelinates axons from multiple brain regions, while some (25%) oligodendrocytes predominantly ensheath axons derived from a particular brain region (motor cortex or senso- ry cortex, “ And, regrettably we don’t have any estimation of how many neurons per oligodendrocyte we are here talking about. With astrocytes, it has been found that one singe astrocytes may contact thousands and even hundreds of thousands of neurons. For reasons below we don’t guess..and that’s all we can do..that the numbers would be that great for oligodendrocytes..but this is part of any picture that our theory is ever going to sketch out for us.

Our model, as most readers here might know , is heavily based on an overall view of the brain as highly dependent each day and in every way on neurogenesis and the advent of new cells or all types, neurons, astrocytes and oligodentrocytes…and then considered what the common origins and nature of that originating process from pluipotent progenitors cells sequested and blooming in those neurogenic niches might be.

So what does that mean to us? The rest of that story?

First of all, as we marvel at the incredible events of neurogenesis ()which until as recently as ten years ago was DENIED by medical science and the publications of indications to the contrary not even finding their way into publications without a struggle) we realize that the process is rather well and interestingly structured.

Simplifying the “road map” here a bit, we do know that the original cells that arise from the pluripotent progenitor milieu…as in the Sub ventricula Zone and the Dentate Gyrus, for most such cells, the earliest cell type that is see is the “radial glia”.

Radial glia – from boring cables to stem cell stars
http://dev.biologists.org/content/140/3/483

Here we summarize a Comparison between the ‘old’ and ‘new’ models of corticogenesis.(see our photo diagram for how this works

(A) In the traditional view, radial glia (cells with long processes that span the whole apicobasal axis of the neuroepithelium; shown in green), were viewed as cables for guiding migrating neurons (red), and were thought to transform into glial cells at later stages of development. (B) The discovery that radial glia were proliferative and gave rise to neurons led to a new concept whereby radial glial cells are the majority of stem and progenitor cells in the ventricular zone, comprising specified neuronal (red) and glial (green) progenitors as well as bi-/multi-potent stem cells (purple).

These radial glial cells are similar to some extend to astroctyes but are not yet astrocytes….they evenually go on to become astrocytes. However that is not all they become. Through a series of stages or repeated division and “asymmetrically” each cell produces another one of its’ own kind” as well as one of its offspring being destined to mature along the path to either a neuron or an oligodendrocyte. Thus what we have are untold numbers of cells in the brain….of all three kinds, astrocytes, neurons, and oligodendrocytes…all emerged from the same ancestry, the same parent cell. NOW, THAT IS TRULY AMAZING. AND IMPORTANT

The brain is actually very much a clonal matrix, where offspring cells are siblings….even though they appear to be of different type…glia (astrocytes or oligodendrocyte) or all those neurons entangled and working with either of those glia.

To this extent they may and likely do have some bit of genomic content distinctly different from all the other cells ostensibly of the same type. The question that then has to arise is that, surely if the offspring of the same ancestry and derived from the same clonal beginnings are to find their way in the world of the brain then isn’t their common origin an and their likey genomic differences from those offspring of different other radial glia…(and indeed different other radial glia being molded epigenetically by reason of different positioning within the SVZ and the immediate signals in that neurogenic niche).

Surely does not that merit consideration (and we believe ‘much more than that”) in understanding how the various neuronal assemblies (all so related to given astrocytes and now related to given oligodendrocytes arise in our brains.

Heretofore, the prevailing way of looking at the brains’ neuronal assemblies has been Hebbian, that is, almost the equivalent of the philosophy of centuries ago where the mind was a blank slate…and whatever caused our minds to grow and think and have ideas of the world was due strictly to the input of an extraneous sort from the outside world.

The Hebbian account of the manner in which neuronal assemblies manage to “form” and coalesce is very much like that old fashioned philosophy going back centuries. Activations of one kind or another are considered the gudiing principle for the “coming together” and joint functioning of these assemblies. Yet…there is no adequate principle for explaining how these “assemblies”, remain distinct from one another other than via some standard electrically modeled activation process..nor how they might arise in the first place. (PS: Do we really wonder long at why it is that such a simplistic model for the arisal of assemblies via activation along never seems to work)

For those who may be curious, there is yet one more aspect of this story which echoes so strongly of Darwinian thinking and the necessity for bringing that to bear in the examination of our brains.There is talk of ‘neurogenesis”…and There is plenty of talk nowadays of “neurogenesis”…and even more “talk relating neurogenesis to the actions of stem cells and the progenitors” that are produced everywhere else in our bodies (although the names of all the cells are typically not indicative that the same process is going on..and the names of signalng molecules are set up perversely so that we don’t always see that the same molecules and regulators are involved)

Yet what is not talked about is how the vast majority of these pluripotent cells are killed off and never see the light of day, millions of them, never make to the stages of which we have been talking here….and on the road to becoming either astroctyes, neurons, or oligodendrocytes. There is a vast literature now exploding on the nuances that arise as this materution and growth process continues in us at every moment of every day with every new experience.

Clearly what we are suggesting here, as part of our “model” is that within the “world” of the brain…which is indeed a “world” and not some computer like system of representations and rules….but an organic world which undergoes birth and death all the time and which manages to be organized by BOTH outside activations that nurture the growth and survival of its assemblies…as well as by the Nature of its cells or inhabitants

Additionally, good “scientific common sense” would dictate that when we speak of “nature” in terms of a genome we also have to consider “epigenetic” modulation of the expression of the genes…and that this modulation has been shown to be a very likely determinant of what happens to those pluripotent progenitor cells and those first radial glia…that spread their tentacles through out our brain…and spin off in clonal manner all sort of other cells. They too are likely candidates for evincing the consequences of those early epigenetic modulations of expression in their own “womb” just as we are all impacted by that epigenetic process in the wombs of our mothers.

The principle “axiom” of life is …in some way…an illusion as we say all too comp;lacently we look at and see “living beings” and “living brains’ and so on. It is actually on every level composed of more than the drama of life and death. but composed of “life, reproduction, and death” and there are Darwinian modes of understanding and dealing with this key aspect of “organisms”..that they “divide” and “reproduce” and that that their “offspring” are not randomly related to their parentage.

One of the problems of the computur metaphor…and a problem with which it afflicts our other studies of the brain is that is does not understand the brain as a “living milieu” with life and death occurring at all time..and not as a “static” mechanism That in fact is the underlying basis of the difference between the concepts “life” and the machines. Life is in constant flux of birth, reproduction and death..on all levels, while machines are “static” and simply function over and over again.

So, do we have an answer to what is going on. Regrettably we are not members of the “academic club’…but we do have questions..that we ask…and all those researchers should…and one day, we are certain, will….be asking. Those questions, by the way, point to a model way beyond the superficial depiction of the brain as some sort of “mechanistic” device…even one as sophisticated as today’s best AI, but instead inexorably lead us to understand the brain as part of our organism and to be functioning very much in accord with the dictates of “life”.

That we believe is the rest of the story….or at least the first page or two.

PS: We have really just written this blog basically “off the top of our heads” while having brunch after a long Saturday night. We promise to insert enough links to other research here (sooner rather than later) to those who wish to delve into this Real Story behind the medical paparazzi story can do so. Of course, all the key words are here…and “Radial Glia” is a great one to commence with.

2 comments

  1. i love radial glia stuff and axons..due to a longstanding puzzle on brain morphology…I posted a select collection of links on timing control at the bottom of this post, but aside from my own wild theorising ive summarised the best from the papers on this. mostly doug fields stuff.

    http://www.lanzalaco.org/2015/06/em-solitons-proven-in-brains-axons-one.html

    But overall we are looking at some type of multiplexing control in the brain, and axon bundles have to be in sync. Just like multiplexing in modern communication systems. Well to put it in context its already accepted the cortical-hippocampal loop is multiplexed. i.e. lisman. This is a classic, and recent follow up works have proven it does occur.

    http://www.jneurosci.org/content/18/24/10688

    ak.. bed time, and university tomorrow.. well good to see such an eclectic collection of subjects to my neuro tastes here

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    1. Hety thanks for the refs on the classic article on radial glia and Ca waves…and gap junctions. It is a great one..and I’m disappointed I missed it. I had to infer and hope for much of what they actually demonstrated as being highly likely. This is an article that offers much further ground for discussion…and beyond neuroscience by to evolution theory and the nature of the brain. Thanks again.

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