Hierarchical Brain

An explanation of the human brain

First published 1st February 2024. This is version 1.5 published 2nd March 2024.
Three pages are not yet published: sleep, memory and an index.
Copyright © 2024 Email info@hierarchicalbrain.com

Warning - the conclusions of this website may be disturbing for some people without a stable mental disposition or with a religious conviction.


Glia is the generic name for a huge number of cells of several different types that are found in the brain. They provide support and maintenance for neurons and synapses and are involved in chemical signalling, but they do not perform electrical signalling like neurons.

Glia cells have often been overlooked in the past as being simply support cells, but it now seems possible that the unique nature of some types of glial cells found only in the brains of human and other higher mammals is one of the things that has contributed to the evolutionary improvement of the brain. It also seems likely that in the near future we will have treatments for a number of brain disorders that involve drugs acting on glial cells.

References For information on references, see structure of this website - references

  1. ^ ^ How many neurons do you have? Some dogmas of quantitative neuroscience under revision - Lent, Azevedo, Andrade-Moraes and Pinto 2011
    doi:10.1111/j.1460-9568.2011.07923.x downloadable here or see GoogleScholar.
    Page 5, second paragraph: “For glial cells, the prevalent dogma poses that the glia/neuron ratio is approximately 10:1 in the brain. However, with the isotropic fractionator, the actual glia/neuron ratio for the whole human brain was shown to be close to 1.”
    Page 5, fourth paragraph: “Glial cells cooperate with neurons in the proper function of the nervous system. Their importance has increased recently, well beyond the early conception of their role as a structural 'glue' for the tissue. During development, glial cells act as stem cells and as guidance scaffolds for migrating neurons and growing axons. In adults, they play important roles in synapse physiology, neurovascular interactions, immune mechanisms and circuit stabilization, signal conduction, fiber maintenance and regeneration, and higher information processing. As a whole, the evidence indicates that glial cells do participate actively in the functional computations performed by neurons, circuits, and networks.”
  2. ^ The interplay between neurons and glia in synapse development and plasticity - Stogsdill and Eroglu 2018
    doi: 10.1016/j.conb.2016.09.016 downloadable here or see GoogleScholar.
    Figure 2 at the bottom of page 5 is a useful summary of some of the latest findings. The figure description says: “(a) Synapse formation is controlled by several astrocyte and microglia-derived soluble factors. Astrocyte secreted factors regulate synapse formation ... BDNF released from microglia also control excitatory synapse formation presumably by binding to the TrkB receptor in neurons. The recruitment of pre and postsynaptic specializations is a key step in synapse development regulated by glia. (b) Synaptic plasticity is controlled by several glial mechanisms. Astrocytes regulate synaptic integration through vesicular release of D-serine and potentially via other factors. Synaptic plasticity is regulated in the visual cortex by astrocytic hevin and microglial P2Y12. (c) Elimination of weak synapses is controlled by microglia through the complement proteins C1q, C3 and C4 and their microglial receptors. Astrocytes engulf and remove unwanted synapses via MEGF10 and MERTK pathways.”
  3. ^ A Competitive Advantage by Neonatally Engrafted Human Glial Progenitors Yields Mice Whose Brains Are Chimeric for Human Glia - Windrem, Schanz, Morrow, Munir, Chandler-Militello, Wang and Goldman 2014
    doi:10.1523/JNEUROSCI.1510-14.2014 downloadable here or see GoogleScholar.
    Page 16159, right-hand column, second sentence under the heading “Discussion”: “We found that a large proportion of glial cells within the recipient mice, often all GPCs and a large proportion of astrocytes, and oligodendrocytes as well, when using hypomyelinated hosts, were ultimately replaced by human donor-derived cells. The extent of this colonization of the mouse brain by human glia appeared so robust that we quantitatively evaluated the absolute numbers, relative proportions, and geographic distributions of human donor cells in the neonatally engrafted recipients.”
    ...continuing on page 16160, right-hand column: “As a result, the greater structural complexity of human astrocytes relative to those of rodents is accompanied by functional differences: human astrocytes propagate Ca2+ wave significantly faster than rodents, and human glial chimeric mice exhibit both enhanced long-term potentiation and facilitated learning in a variety of conditioned response paradigms and cognitive tasks.”
  4. ^ Microglia: New Roles for the Synaptic Stripper - Kettenmann, Kirchhoff and Verkhratsky 2013
    doi: 10.1016/j.neuron.2012.12.023 downloadable here or see GoogleScholar.
    Page 10, third sentence of abstract: “In the normal brain microglia were considered 'resting', but it has recently become evident that they constantly scan the brain environment and contact synapses. Activated microglia can remove damaged cells as well as dysfunctional synapses, a process termed 'synaptic stripping.' Here we summarize evidence that molecular pathways characterized in pathology are also utilized by microglia in the normal and developing brain to influence synaptic development and connectivity, and therefore should become targets of future research.”
  5. ^ Synaptic Pruning by Microglia Is Necessary for Normal Brain Development - Paolicelli et al. 2011
    doi: 10.1126/science.1202529 downloadable here or see GoogleScholar.
    Page 1456, third sentence of abstract: “Here, we show that microglia actively engulf synaptic material and play a major role in synaptic pruning during postnatal development in mice.”
  6. ^ Oligodendrocyte Development and Plasticity - Bergles and Richardson 2016
    doi: 10.1101/cshperspect.a020453 downloadable here or see GoogleScholar.
    Page 1, first paragraph of main text: “Oligodendrocytes (OLs), the myelin-forming cells of the central nervous system (CNS), develop from glial progenitor cells, known as 'oligodendrocyte precursor cells' (OPCs), which arise from several parts of the ventricular germinal zones of the embryonic neural tube. OPCs proliferate and migrate away from these zones into developing gray and white matter before differentiating into myelin-forming OLs. However, unlike most progenitors, OPCs remain abundant in the adult CNS, where they retain the ability to generate new OLs that allow rapid regeneration of myelin that might be lost through normal aging or disease, as well as changing the pattern of myelination in response to life experience.... OPCs have also been referred to as 'NG2 cells' (because they express the NG2 proteoglycan on their surface)...”
    Page 12, first paragraph: “...there has been a recent report that OPCs can produce new neurons in the adult hypothalamus...”
  7. ^ Lineage, Fate, and Fate Potential of NG2-glia - Nishiyama1, Boshans, Goncalves, Wegrzyn and Patel 2016
    doi: 10.1016/j.brainres.2015.08.013 downloadable here or see GoogleScholar.
    Page 1, first paragraph of introduction: “NG2 cells represent a fourth resident glial cell population in the mammalian central nervous system (CNS) that is distinct from astrocytes, mature oligodendrocytes, and microglia. They are defined as non-neuronal, non-vascular glial cells in the CNS parenchyma that express the NG2 antigen and the alpha receptor for platelet-derived growth factor (Pdgfra). They are distributed widely throughout both gray and white matter. They generate oligodendrocytes in culture and in vivo and hence are often equated with oligodendrocyte precursor cells (OPCs).”
  8. ^ The Other Brain - Douglas Fields, speaking on The Leonard Lopate Show on WNYC radio on January 22nd 2010.
    Particularly 4'05" in podcast: “Glia communicate with chemical signalling, and they communicate by sending waves of calcium ions from one cell to another.”

Page last uploaded Sat Mar 2 02:55:42 2024 MST