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Curt Mazur

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Another intuitive but incorrect assumption about the brain is that neurons are sufficient to describe brain function

For 100 years neuroscientists have been trying to describe the function of the brain by examining in exqisite detail the function and circuitry of the neuronal network. This has proved to be insufficient to describe the function of the brain. The majority of the brain, the glial cells, have been almost completely ignored in these descriptions. Although neurons are important, like roads are important to cities, they cannot be used to describe the function of the brain any more than the roads of Los Angeles can be used to describe that city. I feel it is time to incorporate Astrocytes, microglia and oligodendrocytes into the Theory of the Brain.

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    Gabo Moreno 100+

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    May 19 2012: These cells (glia) are taken into account at least since I last took a course in cell biology. At least 13 years ago. If not before.
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    Linda Taylor 50+

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    May 18 2012: Good point. However I have always thought of the astrocytes, micro glia, and oligodendorcytes as the plant operations and housekeeping departments. And when they go awry, there are problems with maintenance and waste removal of the brain. Of course, that results in pathology but how do you see these cells as contributing to the 'function' of the brain?

    • Curt Mazur

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      May 18 2012: I find it interesting that across mammalian species, including humans, the neuronal "wiring patterns" are very similar but changing in scale. This suggests to me that wiring is insufficient to describe the differences between a mouse and a human. If however, you examine the relative Astrocyte cell number to neuron number ratios accross mammalian species you find that with increasing species intelligence there are increasing astrocyte to neuron numbers, meaning that the ratio is higher in a Human compared to a monkey;; higher in a monkey compared to a dog, etc. There is also evidence of cell to cell communication between groups of astrocytes in "calcium waves" and they connect at synapses with the same neurotransmitter receptors as the neurons have. I think that the Astrocyte may be the cell that stores the external stimuli coming in from the environment.
      On the topic of microglia: there is ample evidence that microglia have multiple phenotypic states and change between them based on the condition of the surrounding brain tissue. Additionally microglia in their "resting" state are immensly ramified and a single microglia makes contact with many different synapses, nodes of Ranvier and cell bodies. At this same "resting" state they express genes that are probably involved in synaptic remodeling and neuroplasticity. I see them as the "Electricians of the CNS."
      One more topic for this lengthy response: Oligodendrocytes are the cells that myelinate axons allowing them to transmit action potentials more efficiently. It has been found recently that oligodendrocytes can sense when an action potential has occurred and may respond by adding more myelin to the axon. With the relational minds that humans have I can see this as a central mechanism in the formation of memory and creative thought.
      All of these cells working together allow our brains to make connections between external stimuli and previous experiences to allow the predictions that Hawkins spoke about.
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        Linda Taylor 50+

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        May 18 2012: OK had to think about this for a bit especially when you said that maybe astrocytes store external stimuli. I might buy into that theory if you said that the astrocytes in the amygdala store external stimuli. I mean, that's where that data comes into. As far as the calcium waves,researchers have some data in vitro but have yet to find out about in vivo. That being said, most cells have some mechanism of communication with each other. Much like the compliment system or chemotaxis. And as microglia have some macrophagic function, there may be some connection between calcium waves in the brain and the chemotaxis. Yes we have a higher ration of astrocytes than lower life forms, but they not only provide structure to the brain but they maintain it. They connect to the blood vessels and are responsible for the main waist removal and homeostasis of the entire system. But I really would be hard pressed to think they have much to do with memory storage. They regulate blood flow, fluid and electrolyte balance, and do a lot of maintenance. You could convince me that they are responsible for removing alcohol and the resultant headache.

        Microglia move around. They are like the security force. They check for damage, they clear out any damaged cells. They maintain synaptic spaces. They are immune cells. Myeloid in origin. So they patrol on a regular basis and go to areas of trouble. As myleoid cells I am pretty sure they respond to similar stimuli as their counterparts in the rest of the body. They are probably mobilized through chemotaxis and immune modulators. Maybe astrocytes have the ability to release these immune modulators.

        And yes, oligodendrocytes myelinate axons and specific types of ogliodendrocytes are implicated in certain diseases such as Schwann cells. But they are implicated in memory only in their function and ability to protect the neural cells that store the memory. You would have to come up with some evidence that they have that ability

        • Curt Mazur

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          May 19 2012: I am not sure what you mean by the external stimuli coming into the amygdala? Generally the wiring diagram suggests flow of information from sensory systems and then through the filtering systems of the thalamus and up into the appropriate regions of the cortex. Occipital for optic, generally temporal (and parietal) for auditory, somatosensory for touch etc. Please check out my reading list that I posted below for in depth discussions on these topics. The Other Brain by Fields is quite good and well referenced. I guess my basic point is that trying to explain brain function with only neurons has proven to be problematic at best and we should try to incorporate the other cells which make up the majority of the brain, in the scheme. I can't imagine that nature would be so wasteful to have 90% of the brain as basically non-functioning support for the 10% that are neurons. Also neurons are quite static when you think about it, they can't reproduce or re-sprout, the best you can hope for them to do is long term potentiation. Whereas the glia cells are much more dynamic, can divide, change morphology etc. If one just thinks about the dynamic nature of thought and memory, without any pre-concieved notions of how the brain functions, one may think that the cells responsible for this process are the dynamic ones (glia) and not the static ones (neurons). More on this in my next post

        • Curt Mazur

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          May 19 2012: My point on oligodendrocytes is that when thinking about how human (and probably other mammalian) thought and memory occurs it is relational. An analogy of this is that if your cones of your retina register 50% blue and 50% yellow then send that through the various brain structures to your optic cortex, it then gets registered there as a combination that has been seen before. This is then relayed to your language cortex as a set of sounds that you have previously correlated with that combination "Green". When you were born that connection wasn't there and through repetition the connection has been made stronger so that almost instantaneously when your optic cortex registers the 50% blue and 50% yellow you immediately think "green." I think that as this connection is made repeatedly the oligodendrocytes of those axons that make that connection sense the change in voltage at the Nodes of Ranvier and lay down more myelin, thereby making the connection that much faster, to the point where it is almost instantaneous. Certainly oligodendrocytes are involved in multiple sclerosis as that is a demyelinating autonomic disease.
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        Linda Taylor 50+

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        May 19 2012: For a quick diagram of amygdala and sensory processing.
        http://www.scholarpedia.org/article/File:Amygdala_Figure_5.gif
        And it is part of what is called the reptilian complex. I always think of it that way because it is integral to survival of our species. It is implicated in fight or flight and all senses are integrated in it. It can make you act before you think as part of our reflexes for survival. So it takes in sensory stimuli and if it is aversive, puts you in survival mode. So if astrocytes were to keep some type of sensory stimulus, that would maybe be a place to look. It happens way before anything hits the cerebral cortex. (Understand this is Linda Taylor's understanding of how it works. I'm sure there's some neuroscientist that can explain better.

        And as far as the eye, the cones are stimulated by wavelength, not percentage of blue or green. When the cones are stimulated, they send an action potential along a neuron. Not a microglial cell or an astrocyte, a neuron.

        I really don't understand why you think that 90% of the brain is non functioning. The whole point of astrocytes is to provide structure and make the brain possible. That's like saying bones are not functional because they don't contract like muscles do.

        Like I said, microglia are myeloid in origin. They are no more a part of brain function than white blood cells are to the process of walking. They are immune cells and are important in the maintenance of the entire thing but they are not part of what the brain actually does. They are on patrol.

        The oligodendrocytes are also maintenance workers. They make sure the wiring does not short out. But that does not mean they are involved in conducting the electricity. They are analogous to osetoblasts. They create but do not contribute to the structure.

        I really haven't read your citation and frankly hesitate to do so. There are some huge problems with this type of interpretation of brain function.

        • Curt Mazur

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          May 19 2012: Linda I am asking that you open your mind and please take off your neurocentric blinders. Neuroscience has pursued the same doctrine for 100 years since Ramon y Cajal gave his Nobel acceptance speech and we still are not able to develop a theory of how the brain works by neurons alone. I understand that cones are stimulated by wavelengths of light I was simply using the 50% blue and 50% yellow as an analogy, in a green field of view say 50% of the cones that respond to blue light and 50% of the cones that respond to yellow light are stimulated. I realize that the action potential travels along a neuron but where does the information go? Have you ever looked at neuronal staining in the cortex? the dendrites of the different neuronal layers of the cortex terminate in layers of astrocytes. There is a term called the tripartite synapse where neurons, astrocytes and microglia all connect at synaptic junctions. What are they doing there? As far as microglia are concerned, they are very dynamic cells that because of their myeloid origin can modulate different cellular processes by producing and releasing bioactive molecules. Also because of their myeloid origin they can transform into multiple phenotypes to do multiple types of jobs. The amygdala is a central structure for the processing of emotions and may work as some sort of filtering mechanism similar to those in the thalamus. It is a connection between the brainstem, hippocampus and cortex that as you said is involved with the fight or flight reptilian responses. I am not saying that 90% of the brain is non-functioning, in fact I am saying the opposite: why would nature waste 90% of the brain mass to "support" the 10% elite neurons? It makes no sense to me. Also the cellular structure of the brain is highly conserved throughout evolution. Your statement at the end bothers me the most, why wouldn't you want to read the literature that I suggested and choose for yourself?
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        Linda Taylor 50+

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        May 19 2012: Curt
        I do not have neurocentric blinders. But even Mr. Hawkins in his one man commercial for artificial intelligence, stated that any theory had to be biologically realistic.

        So you have the tripartite junction where all connect. Since astrocytes connect to blood vessels and neurons do not, perhaps there is some type of nourishment system or some type of supply chain. There are a lot of ions involved in an action potential. Where do you think those ions come from? And neurotransmitters, do we think they just magically appear in the synaptic junction? And perhaps the microglia in their role as sentry, are monitoring for the possibility of micro organismic invasion. Or maybe they help clean up excess neurotransmitters. That makes way more sense than astrocytes storing environmental stimuli.

        I also asked you what you thought the role of those cells were in the 'function' of the brain and you bought into the whole Hawkins definition of prediction. Fine, I can play there even though I think there are real problems with what he is saying. It just does not make biologic sense that those cells are involved in prediction. But I am willing to entertain the idea.

        I completely understand that only 10 % of the brain is neurons. But the other 90% not only provides structure but is involved in system monitoring. I mean your entire organism monitoring. When should you take a breath, how fast, do we need more blood in our brain or in our muscles right now. Perhaps the monitoring function of the brain is way more important than the do function of the brain.

        The only reason I hesitate to delve into your references is that I happen to be a busy person and the I have to consider the efficacy of of my activities. I am not all that interested in childhood schizophrenia but I might consider reviewing articles by Dr. Fields and Dr. Koob. But I am not going to buy their book. Show me the dat
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    Gerald O'brian 50+

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    May 18 2012: And what reading do you recommend, then, to the layman?

    • Curt Mazur

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      May 18 2012: The Other Brain by Douglas Fields, and The Root of Thought by Andrew Koob. You should read The Root of Thought initially and then The Other Brain as this will allow the presentation of the basic ideas by Koob before the more detailed descriptions by Fields
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