The smart mouse with the half-human brain

Mice with human glial cells

Studies of mental functions, behaviors and the nervous system.

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Re: The smart mouse with the half-human brain

#21  Postby DavidMcC » Dec 04, 2014 5:01 pm

You seem to think that that makes them neurons, but that would be inaccurate:
http://en.wikipedia.org/wiki/Neuroglia
Glial cells, sometimes called neuroglia or simply glia (Greek γλία, γλοία "glue"; pronounced in English as either /ˈɡliːə/ or /ˈɡlaɪə/), are non-neuronal cells that maintain homeostasis, form myelin, and provide support and protection for neurons in the brain and peripheral nervous system.[1]

As the Greek name implies, glia are commonly known as the glue of the nervous system; however, this is not fully accurate. Neuroscience currently identifies four main functions of glial cells:

To surround neurons and hold them in place
To supply nutrients and oxygen to neurons
To insulate one neuron from another
To destroy pathogens and remove dead neurons.

For over a century, it was believed that the neuroglia did not play any role in neurotransmission. However 21st century neuroscience has recognized that glial cells do have some effects on certain physiological processes like breathing,[2][3] and in assisting the neurons to form synaptic connections between each other.[4]

The last sentence probably explains the confusion caused by the fact that glial cells can generate action potentials.
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Re: The smart mouse with the half-human brain

#22  Postby GrahamH » Dec 04, 2014 6:58 pm

David I note you are shying the expert opinion presented without providing reasons. Why?
The Wikipedia article you linked goes further:
In the past, glia had been considered[by whom?] to lack certain features of neurons. For example, glial cells were not believed to have chemical synapses or to release transmitters. They were considered to be the passive bystanders of neural transmission. However, recent studies have shown this to be untrue.
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Re: The smart mouse with the half-human brain

#23  Postby DavidMcC » Dec 05, 2014 1:05 pm

GrahamH wrote:David I note you are shying the expert opinion presented without providing reasons. Why?
The Wikipedia article you linked goes further:
In the past, glia had been considered[by whom?] to lack certain features of neurons. For example, glial cells were not believed to have chemical synapses or to release transmitters. They were considered to be the passive bystanders of neural transmission. However, recent studies have shown this to be untrue.

If you read even further, you find that there is reason to believe that this particular "expert opinion" is not supported by other experts:
For example, astrocytes are crucial in clearance of neurotransmitters from within the synaptic cleft, which provides distinction between arrival of action potentials and prevents toxic build-up of certain neurotransmitters such as glutamate (excitotoxicity). It is also thought that glia play a role in many neurological diseases, including Alzheimer's disease. Furthermore, at least in vitro, astrocytes can release gliotransmitter glutamate in response to certain stimulation.

I understand this to mean that glial cells do not function as neurons, but in support of neurons (by which I do not mean merely mechanical support). Note the word, "gliottransmitter", not "neurotransmitter". I take that to mean that they do not take part directly in neuron circuit function, except to limit the possible damage due to their toxic build-up.

EDIT: I didn't quote more, because I didn't think you would misinterpret it the way you apparently did.
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Re: The smart mouse with the half-human brain

#24  Postby GrahamH » Dec 06, 2014 9:26 am

DavidMcC wrote:
GrahamH wrote:David I note you are shying the expert opinion presented without providing reasons. Why?
The Wikipedia article you linked goes further:
In the past, glia had been considered[by whom?] to lack certain features of neurons. For example, glial cells were not believed to have chemical synapses or to release transmitters. They were considered to be the passive bystanders of neural transmission. However, recent studies have shown this to be untrue.

If you read even further, you find that there is reason to believe that this particular "expert opinion" is not supported by other experts:
For example, astrocytes are crucial in clearance of neurotransmitters from within the synaptic cleft, which provides distinction between arrival of action potentials and prevents toxic build-up of certain neurotransmitters such as glutamate (excitotoxicity). It is also thought that glia play a role in many neurological diseases, including Alzheimer's disease. Furthermore, at least in vitro, astrocytes can release gliotransmitter glutamate in response to certain stimulation.

I understand this to mean that glial cells do not function as neurons, but in support of neurons (by which I do not mean merely mechanical support). Note the word, "gliottransmitter", not "neurotransmitter". I take that to mean that they do not take part directly in neuron circuit function, except to limit the possible damage due to their toxic build-up.

EDIT: I didn't quote more, because I didn't think you would misinterpret it the way you apparently did.


You understand it to mean what you want it to mean. What it actually says does not contradict the other quote at all. Where is the contradiction? Quote one says glial cells do A,B & C. Quote two says glial cells do X, Y, Z. So this is entirely consistent with glial cells doing A, B, C, X, Y & Z. Nowhere does quote two say glial cells do not do A,B or C, nor that glial cells do only X,Y & Z.
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Re: The smart mouse with the half-human brain

#25  Postby DavidMcC » Dec 06, 2014 2:37 pm

So you still don't get it, then. Nowhere does the article claim that glial cells do anything more than to protect neurons and help them work efficiently. Apart, that is, from playing a more active role than previously recognised in some autonomic functions, such as breathing:
Ref. 2 in the Wiki article: http://discovermagazine.com/2011/jan-feb/62
In a report published in Science in July, British and American researchers showed that when rats inhale excess carbon dioxide, astrocytes in the brain stem sense the resulting increase in blood acidity. The team tagged these astrocytes with a protein that fluoresces in response to cellular activity and saw that the cells signaled the neurons that influence breathing. The rats then breathed more deeply, taking in more oxygen. “These guys are even more sensitive than neurons,” says Sergey Kasparov, a University of Bristol molecular physiologist.

OK, so they give the neurons a nudge when autonomic functions are at risk, but they don't signal the lungs. In other words, the article is claiming that the glia protect neurons in the autonomic system in a more pre-emptive fashion than was previously recognized, in order to better protect them (and their owner!).
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Re: The smart mouse with the half-human brain

#26  Postby DavidMcC » Dec 06, 2014 2:54 pm

GrahamH wrote:...
You understand it to mean what you want it to mean. What it actually says does not contradict the other quote at all. Where is the contradiction? Quote one says glial cells do A,B & C. Quote two says glial cells do X, Y, Z. So this is entirely consistent with glial cells doing A, B, C, X, Y & Z. Nowhere does quote two say glial cells do not do A,B or C, nor that glial cells do only X,Y & Z.

It isn't a question of what I WANT it to mean, only of what I THINK IT DOES mean, OK?
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Re: The smart mouse with the half-human brain

#27  Postby GrahamH » Dec 06, 2014 3:17 pm

DavidMcC wrote:
GrahamH wrote:...
You understand it to mean what you want it to mean. What it actually says does not contradict the other quote at all. Where is the contradiction? Quote one says glial cells do A,B & C. Quote two says glial cells do X, Y, Z. So this is entirely consistent with glial cells doing A, B, C, X, Y & Z. Nowhere does quote two say glial cells do not do A,B or C, nor that glial cells do only X,Y & Z.

It isn't a question of what I WANT it to mean, only of what I THINK IT DOES mean, OK?


What it does mean was clear to me, if not to you. I pointed that out, indeed spelled out the reasoning so that a child could follow it, but you haven't responded to that or offered any justification for you claim to have posed an expert dissent or counter argument to expert claims about sophisticated capabilities of glial cells.
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Re: The smart mouse with the half-human brain

#28  Postby DavidMcC » Dec 07, 2014 1:13 pm

GrahamH wrote:
DavidMcC wrote:
GrahamH wrote:...
You understand it to mean what you want it to mean. What it actually says does not contradict the other quote at all. Where is the contradiction? Quote one says glial cells do A,B & C. Quote two says glial cells do X, Y, Z. So this is entirely consistent with glial cells doing A, B, C, X, Y & Z. Nowhere does quote two say glial cells do not do A,B or C, nor that glial cells do only X,Y & Z.

It isn't a question of what I WANT it to mean, only of what I THINK IT DOES mean, OK?


What it does mean was clear to me, if not to you.
You may think it is obvious that the article means that glial cells act as neurons, but I insist that that is not so. It means that they communicate with neurons, but only for the sake of the latter's health and welllfare. It's simple, really.
I pointed that out, indeed spelled out the reasoning so that a child could follow it, but you haven't responded to that or offered any justification for you claim to have posed an expert dissent or counter argument to expert claims about sophisticated capabilities of glial cells.

The capabilities of glial cells are, indeed, sophisticated, but that does not nean that they control neurons, except to the extent of keeping them out of harm's way, as far as possible.
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Re: The smart mouse with the half-human brain

#29  Postby GrahamH » Dec 07, 2014 1:40 pm

DavidMcC wrote:
GrahamH wrote:
DavidMcC wrote:
GrahamH wrote:...
You understand it to mean what you want it to mean. What it actually says does not contradict the other quote at all. Where is the contradiction? Quote one says glial cells do A,B & C. Quote two says glial cells do X, Y, Z. So this is entirely consistent with glial cells doing A, B, C, X, Y & Z. Nowhere does quote two say glial cells do not do A,B or C, nor that glial cells do only X,Y & Z.

It isn't a question of what I WANT it to mean, only of what I THINK IT DOES mean, OK?


What it does mean was clear to me, if not to you.
You may think it is obvious that the article means that glial cells act as neurons, but I insist that that is not so. It means that they communicate with neurons, but only for the sake of the latter's health and welllfare. It's simple, really.
I pointed that out, indeed spelled out the reasoning so that a child could follow it, but you haven't responded to that or offered any justification for you claim to have posed an expert dissent or counter argument to expert claims about sophisticated capabilities of glial cells.

The capabilities of glial cells are, indeed, sophisticated, but that does not nean that they control neurons, except to the extent of keeping them out of harm's way, as far as possible.

Yet again you offer opinion without justification or evidence. I am well aware that you don't like the idea that glial cells play an active role in signalling and intelligence, but you have presented nothing to contradict those studies that suggest you are wrong.
Why do you think that?
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Re: The smart mouse with the half-human brain

#30  Postby DavidMcC » Dec 07, 2014 1:55 pm

GrahamH wrote:
DavidMcC wrote:
GrahamH wrote:
DavidMcC wrote:
It isn't a question of what I WANT it to mean, only of what I THINK IT DOES mean, OK?


What it does mean was clear to me, if not to you.
You may think it is obvious that the article means that glial cells act as neurons, but I insist that that is not so. It means that they communicate with neurons, but only for the sake of the latter's health and welllfare. It's simple, really.
I pointed that out, indeed spelled out the reasoning so that a child could follow it, but you haven't responded to that or offered any justification for you claim to have posed an expert dissent or counter argument to expert claims about sophisticated capabilities of glial cells.

The capabilities of glial cells are, indeed, sophisticated, but that does not nean that they control neurons, except to the extent of keeping them out of harm's way, as far as possible.

Yet again you offer opinion without justification or evidence. I am well aware that you don't like the idea that glial cells play an active role in signalling and intelligence, but you have presented nothing to contradict those studies that suggest you are wrong.

What nonsense! I dod not need to present new evidence, because the disagreement is about interpretation of the evidence (concerning the functions of glial cells). You seem to think that linked article show that glial cells control neurons, period! :roll:
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Re: The smart mouse with the half-human brain

#31  Postby GrahamH » Dec 07, 2014 3:44 pm

DavidMcC wrote:
GrahamH wrote:
DavidMcC wrote:
GrahamH wrote:

What it does mean was clear to me, if not to you.
You may think it is obvious that the article means that glial cells act as neurons, but I insist that that is not so. It means that they communicate with neurons, but only for the sake of the latter's health and welllfare. It's simple, really.
I pointed that out, indeed spelled out the reasoning so that a child could follow it, but you haven't responded to that or offered any justification for you claim to have posed an expert dissent or counter argument to expert claims about sophisticated capabilities of glial cells.

The capabilities of glial cells are, indeed, sophisticated, but that does not nean that they control neurons, except to the extent of keeping them out of harm's way, as far as possible.

Yet again you offer opinion without justification or evidence. I am well aware that you don't like the idea that glial cells play an active role in signalling and intelligence, but you have presented nothing to contradict those studies that suggest you are wrong.

What nonsense! I dod not need to present new evidence, because the disagreement is about interpretation of the evidence (concerning the functions of glial cells). You seem to think that linked article show that glial cells control neurons, period! :roll:


You haven't shown anything to establish that glial cells don't function as the OP articles suggest they do. You haven't presented anything contradictory to that. Take a moment, calm down and maybe re-read the thread. It goes like this:

Me: links to articles about how glial cells play more than a housekeeping role for neurons. 'Glial cells make you smart'.
You: No, glial cells are only housekeeping for neurons.
Me: Why do you think that?
You: Link to wikipedia section on glial cell houskeeping functions
Me: Same link to glial cells more than houskeeping
You: YOUR opinion that glial cells are just houskeepers
Me: Why do you think that? You haven't justified your opinion.
You: Emotional outburst 'ridiculous! I don't need to present any evidence or contrary expert opinion'.
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Re: The smart mouse with the half-human brain

#32  Postby DavidMcC » Dec 07, 2014 3:55 pm

GrahamH wrote:
DavidMcC wrote:
GrahamH wrote:
DavidMcC wrote:You may think it is obvious that the article means that glial cells act as neurons, but I insist that that is not so. It means that they communicate with neurons, but only for the sake of the latter's health and welllfare. It's simple, really.
The capabilities of glial cells are, indeed, sophisticated, but that does not nean that they control neurons, except to the extent of keeping them out of harm's way, as far as possible.

Yet again you offer opinion without justification or evidence. I am well aware that you don't like the idea that glial cells play an active role in signalling and intelligence, but you have presented nothing to contradict those studies that suggest you are wrong.

What nonsense! I dod not need to present new evidence, because the disagreement is about interpretation of the evidence (concerning the functions of glial cells). You seem to think that linked article show that glial cells control neurons, period! :roll:


You haven't shown anything to establish that glial cells don't function as the OP articles suggest they do. You haven't presented anything contradictory to that. Take a moment, calm down and maybe re-read the thread. It goes like this:

Me: links to articles about how glial cells play more than a housekeeping role for neurons. 'Glial cells make you smart'.
You: No, glial cells are only housekeeping for neurons.
Me: Why do you think that?
You: Link to wikipedia section on glial cell houskeeping functions
Me: Same link to glial cells more than houskeeping
You: YOUR opinion that glial cells are just houskeepers
Me: Why do you think that? You haven't justified your opinion.
You: Emotional outburst 'ridiculous! I don't need to present any evidence or contrary expert opinion'.

Maybe your interpretation (and the original authors') of "housekeeping" is too restrictive. To me, it includes telling the neurons when to take it easy, for their own sake. I don't blame you, I blame the original article, for unclear thinking.
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Re: The smart mouse with the half-human brain

#33  Postby GrahamH » Dec 07, 2014 4:07 pm

:roll:
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Re: The smart mouse with the half-human brain

#34  Postby DavidMcC » Dec 08, 2014 2:37 pm

GrahamH wrote::roll:

I take that to mean that you still think that glial action potentials are evidence of a role for glial cells beyond that of protecting neurons. However, the article has not provided such evidence, even if the authors think that they have. What is new is that the glial cells appaently use action potentials to perform that function. The mistake was becasue action potentials have always been associated only with neural function, not glial function.
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Re: The smart mouse with the half-human brain

#35  Postby GrahamH » Dec 08, 2014 5:44 pm

DavidMcC wrote:
GrahamH wrote::roll:

I take that to mean that you still think that glial action potentials are evidence of a role for glial cells beyond that of protecting neurons. However, the article has not provided such evidence, even if the authors think that they have. What is new is that the glial cells appaently use action potentials to perform that function. The mistake was becasue action potentials have always been associated only with neural function, not glial function.


There were specific claims with references:
Glial cells comprise several distinct populations. In the central nervous system (CNS) these are astrocytes and oligodendrocytes, both of which share a neuroepithelial origin with neurons, as well as microglia, CNS-resident cells of the innate immune system. There is in addition an abundant population of progenitor cells commonly called oligodendrocyte progenitor cells (or OPCs, a term that belies their multipotency). So why are glial cells more than simply brain glue? Without reviewing all the evidence, here are a few examples. (1) As brain size and information processing capacity increases, one would predict a corresponding increase in glia. Yet the increase is disproportionate: on ascending the phylogenetic tree the proportion of glia to neurons increases—this is apparent even within the primates (including humans—Albert Einstein had an especially large number of glia within the brain region responsible for higher-level cognition) (Fields, 2004). (2) In addition to facilitating rapid impulse conduction, oligodendrocytes also provide trophic support for the axons they myelinate, allowing axons to attain longer lengths and hence vertebrates to achieve much greater sizes than would otherwise be possible (Nave, 2010). (3) OPCs can generate action potentials, previously thought to be the sole preserve of neurons and a key function that distinguished them from glia (Káradóttir et al., 2008). This OPC property strongly hints at important physiological functions in the normal CNS in addition to their role in the regenerative process of remyelination (Zawadzka et al., 2010). (4) Astrocytes, a diverse population of cells with multiple functions, maintain and sculpt the synaptic contacts on which CNS function depends (Ullian et al., 2001). All of these relatively recently revealed properties of glia demand an updated concept of brain function in which neurons and glia work as equal partners, interacting in a mutually dependent manner. But what evidence is there that glia might be in the driver’s seat?

Human astrocytes are larger and have a greater morphological diversity than those of rodents, with distinctive subtypes uniquely present in hominids. Thus, there is a correlation between more complex information processing and astrocyte complexity that might be causal. In their current report, Han and colleagues test this theory using an ingenious stem cell (or more specifically progenitor cell) -based approach. Previously, the laboratory of Steven Goldman (one of this study’s senior authors) produced adult mice with a chimeric CNS consisting of mouse neurons (and oligodendrocytes) and human astrocytes and progenitor cells, achieved by engrafting human glial progenitors into the neonatal mouse CNS (Windrem et al., 2008). Large regions of the CNS in these mice, including the hippocampus, consist of mouse neurons surrounded by human astrocytes, thus providing a configuration with which to compare with wild-type mice.

Using this transplantation model in the current study, Han and colleagues addressed the critical question of whether the increasing complexity of human astrocytes confers greater functional abilities. The authors tested the mice on a battery of learning and memory tasks (including Barnes maze navigation, object-location memory, and contextual and tone fear conditioning tasks) and found that the chimeric mice showed enhanced performance on all tests compared to their entirely murine controls. Furthermore, long-term potentiation (LTP), a long-lasting enhancement in signal transmission between two neurons thought to underlie the plasticity necessary for certain types of learning and memory, was enhanced in these animals. These results provide compelling evidence that the greater cognitive sophistication of humans compared to mice is at least in part due to differences in their glia.

By beginning to explore a role for glia in higher cognitive function, this study raises intriguing questions about exactly what, and how extensive, these roles might be; for example, are other domains of cognition affected? Furthermore, it would be of interest to examine the effects of engrafting human glia on other important forms of plasticity, such as long-term depression (LTD). Further exploration of exactly what role glia play in these and in other processes would ultimately be fascinating.

This paper, which promises to be a landmark for glial cell biology, provides a wonderful example of how stem cell biology can be used to address fundamental questions of physiology. In a sense, this study harks back to the early days of glial cell transplantation, where this procedure represented a powerful experimental tool to study how glia interacted with each other and with neurons (Blakemore and Franklin, 1991). The finding that transplanted glial progenitors were able to remyelinate demyelinated axons meant that the technique quickly became diverted toward possible therapeutic objectives, a route which has now crossed the translational chasm, with the publication of the outcome of initial cell therapies for inherited disorders of myelination (Gupta et al., 2012). While these developments are immensely encouraging, it is nevertheless important that the research community fully harness the power of stem cells to explore physiology: this paper provides just such an example, elegantly revealing the functional interplay between neurons and glia. Perhaps, after all, it is neither your neurons nor your glia that make you clever, but both, working in tandem.

http://www.sciencedirect.com/science/ar ... 0913000581


Specifically on the action potentials

A defining feature of glial cells has been their inability to generate action potentials. We show here that there are two distinct types of morphologically identical oligodendrocyte precursor glial cells (OPCs) in situ in rat CNS white matter. One type expresses voltage-gated sodium and potassium channels, generates action potentials when depolarized and senses its environment by receiving excitatory and inhibitory synaptic input from axons. The other type lacks action potentials and synaptic input. We found that when OPCs suffered glutamate-mediated damage, as occurs in cerebral palsy, stroke and spinal cord injury, the action potential-generating OPCs were preferentially damaged, as they expressed more glutamate receptors, and received increased spontaneous glutamatergic synaptic input in ischemia. These data challenge the idea that only neurons generate action potentials in the CNS and imply that the development of therapies for demyelinating disorders will require defining which OPC type can carry out remyelination.


http://www.nature.com/neuro/journal/v11 ... n2060.html
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Re: The smart mouse with the half-human brain

#36  Postby DavidMcC » Dec 09, 2014 1:22 pm

Graham, I would like to point out that the myelination function alone of glials cells would enable longer distance axons, enabling a bigger, better connected brain. I also question the logic of concluding that the evidence presented shows that glia are "in the driver's seat", controlling the neurons, whatever that is supposed to mean. To me, that would be like claiming that road-menders, which enable faster motorway traffic, directly make the cars go faster! I much prefer the statement, "Perhaps, after all, it is neither your neurons nor your glia that make you clever, but both, working in tandem." Such working in tandem does not imply that the glia ARE neurons, and is consistent with their main function being to enable bigger neural circuits, operating better.
BTW, your sugestion that I was somehow making an "emotional outburst", "without evidence" is absurd. I was merely pointing out that your interpretation of the article may have been rather OTT, perhaps encouraged by the wording of the article.
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Re: The smart mouse with the half-human brain

#37  Postby GrahamH » Dec 09, 2014 2:13 pm

You still haven't refuted the claims presented that some glial cells actively signal.
You just keep repeating your opinion.

These data challenge the idea that only neurons generate action potentials in the CNS
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Re: The smart mouse with the half-human brain

#38  Postby DavidMcC » Dec 09, 2014 2:39 pm

GrahamH wrote:You still haven't refuted the claims presented that some glial cells actively signal.
You just keep repeating your opinion.

These data challenge the idea that only neurons generate action potentials in the CNS

Sure, they do, but that is not the same as claiming that the evidence shows that glia control neurons, beyond what is necessary for their own safety and efficiency.
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Re: The smart mouse with the half-human brain

#39  Postby kennyc » Dec 09, 2014 2:46 pm

Holy shit guys, get a room!
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Re: The smart mouse with the half-human brain

#40  Postby DavidMcC » Dec 09, 2014 3:35 pm

Hopefully, that won't be necessary, kenny.

A defining property of neurons that has not been shown to be also a property of glial cells is that which is best summed up as "neurons that fire together, wire together".
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