Laws for Glia Organization Conserved Across Mammals

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Abstract

The organizational principles of glia remain largely unknown despite their vital role in nervous system function. Previous work has shown that the number of glia per unit volume of neocortex is constant across mammalian species. We hypothesize that the conservation of glia volume density within brain regions might be a governing principle of organization across species. To test this hypothesis, we used stereology, light microscopy, and data available in the literature to examine five brain regions: the cerebral cortex and four brain regions that differ from the cerebral cortex and each other - the anterior piriform cortex, the posterior piriform cortex, the entorhinal cortex, and the cerebellum. We discovered two orderly relationships: First, glia volume density within a brain region was constant across species, including humans, although it significantly differed between regions, suggesting that glia density might constitute a region-specific marker. Second, the ratio of glia to neuron increased with brain volume according to a ¼ power law in the primate frontal cortex and the neocortex, the mammalian paleocortex, and the cerebellum. These relationships show that the development of glia and neurons are coupled, and suggest that what a neural circuit computes depends as much on its glial components as on its neurons.

Main Points

  • The volume density of glia (i.e., number of glia per unit volume) within a brain region is con-served across mammalian species including humans.

  • The ratio of glia to neuron increases with bigger brains.

  • The volume density of glia is significantly different across functionally and architecturally dif-ferent brain regions and could function as a region-specific marker.

  • Glia obey scaling constraints that are different from scaling constraints for neurons.

Article activity feed

  1. Thus, glia as well individual glial cell type (spatial) distributionswere broadly similar in mice and humans, suggesting glia as a whole might share somesimilarities in function across species

    Exciting! And a premise many of us that work in mouse models are depending on. I also wonder whether different astrocytic subtypes that have been described as primate-specific may be differentiated in your future assays.

  2. In summary,GNR scale with brain size similarly in APC, prefrontal cortex, and the cerebellum.

    As you're analyzing several glial subtypes together here, this finding brings up several questions, including whether these relationships are driven by a particular glial cell type and whether/how different glial cell type number are determined developmentally relative to each other.

  3. Figure 3: Glia volume densities were constant across species in the APCx.

    Another small note for several figures is that the resolution is low and sometimes it is difficult to read labels (here, especially the species names).

  4. (d) Shows the estimates of the total number of glia cell types measured with DAB and Nisslstains. The DAB staining bar is broken into three sections, each section a different color denoting thethree major glia-types: sox9 in grey for astrocytes, iba1 in light blue for microglia, and oligodendrocytes indark blue for oligodendrocytes. The bar on the right denotes the estimate of total number of glia under amm2 of surface measured in Nissl stains. (e) Shows overall glia and each glial cell type distribution acrosslayers. The Nissl bar shows the total number of glia in every layer, and the other three show the individualdistribution of each glia-type in every layer.

    A small comment on the figure design here is that using the same colors for type of stain (d) and then layer but not stain (e), is a bit confusing.

  5. First, glia density is constant withinthe same circuit, independent of species or brain size. Second, GNRs increase with brain size atthe same rate in different circuits.

    I find the language a little confusing here, especially as it differs between the intro and the results/discussion. Here, I think you're using "circuit" to mean the same thing as brain region, but elsewhere, you use "region". I think consistency would help with clarity.

  6. Previous studies have shown that even thoughastrocytes have large cell bodies

    In several mouse brain regions, my experience with patching astrocytes and neurons in ex vivo brain slices (as well as DIC images in ex vivo slices from many other groups) shows that astrocytes have smaller cell bodies than neurons, and in fact, can be identified solely based on their smaller somata. I bet that the Nissl staining here likely reflects real neuron-astrocyte size differences, as observed in unfixed tissue.

  7. Mus musculus (mouse), Rattus novergicus (rat), Cavia porcellus (guineapig), Mustela putoris furo (ferret), Monodelphis domestica (short-tailed opossum), Felis catus(domestic cat), and Homo Sapiens (humans).

    It's very cool that you were able to obtain tissue from and analyze so many mammalian species, including humans. If you could speculate, do you think you'd find that the same principles you uncovered also hold for non-mammalian vertebrates?