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All brains are made of this: a fundamental building block of brain matter with matching neuronal and glial masses.

Mota B, Herculano-Houzel S - Front Neuroanat (2014)

Bottom Line: We propose that there is a fundamental building block of brain tissue: the glial mass that accompanies a unit of neuronal mass.We argue that the scaling of this glial mass is a consequence of a universal mechanism whereby numbers of glial cells are added to the neuronal parenchyma during development, irrespective of whether the neurons composing it are large or small, but depending on the average mass of the glial cells being added.We also show how evolutionary variations in neuronal cell mass, glial cell mass and number of neurons suffice to determine the most basic characteristics of brain structures, such as mass, glia/neuron ratio, neuron/glia mass ratio, and cell densities.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Física, Universidade Federal do Rio de Janeiro Rio de Janeiro, Brazil ; Instituto Nacional de Neurociência Translacional São Paulo, Brazil.

ABSTRACT
How does the size of the glial and neuronal cells that compose brain tissue vary across brain structures and species? Our previous studies indicate that average neuronal size is highly variable, while average glial cell size is more constant. Measuring whole cell sizes in vivo, however, is a daunting task. Here we use chi-square minimization of the relationship between measured neuronal and glial cell densities in the cerebral cortex, cerebellum, and rest of brain in 27 mammalian species to model neuronal and glial cell mass, as well as the neuronal mass fraction of the tissue (the fraction of tissue mass composed by neurons). Our model shows that while average neuronal cell mass varies by over 500-fold across brain structures and species, average glial cell mass varies only 1.4-fold. Neuronal mass fraction varies typically between 0.6 and 0.8 in all structures. Remarkably, we show that two fundamental, universal relationships apply across all brain structures and species: (1) the glia/neuron ratio varies with the total neuronal mass in the tissue (which in turn depends on variations in average neuronal cell mass), and (2) the neuronal mass per glial cell, and with it the neuronal mass fraction and neuron/glia mass ratio, varies with average glial cell mass in the tissue. We propose that there is a fundamental building block of brain tissue: the glial mass that accompanies a unit of neuronal mass. We argue that the scaling of this glial mass is a consequence of a universal mechanism whereby numbers of glial cells are added to the neuronal parenchyma during development, irrespective of whether the neurons composing it are large or small, but depending on the average mass of the glial cells being added. We also show how evolutionary variations in neuronal cell mass, glial cell mass and number of neurons suffice to determine the most basic characteristics of brain structures, such as mass, glia/neuron ratio, neuron/glia mass ratio, and cell densities.

No MeSH data available.


Neuron/glia mass ratio varies with average glial cell mass across brain structures and species. Graphs show the neuron/glia mass ratio (mnNn/mgNg) as (A) a function of estimated glial cell mass (mg) and (B) a function of the inverse of measured glial cell density (d−1gmes) in each brain structure in each species. Average glial cell mass in picograms; d−1gmes in picograms/neuron. Functions plotted are (A)mn.Nn/mg.Ng = 0.064mg2.433 ± 0.260 (r2 = 0.528, p < 0.0001) and (B)mn.Nn/mg.Ng = 0.132 dgmes−11.072 ± 0.034 (r2 = 0.926, p < 0.0001). Cerebral cortex plotted as circles, cerebellum as squares, and rest of brain as triangles; eulipotyphlans shown in orange, primates in red, and rodents in green. Data from Herculano-Houzel et al. (2006, 2007, 2011), Azevedo et al. (2009), Sarko et al. (2009), and Gabi et al. (2010).
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Figure 13: Neuron/glia mass ratio varies with average glial cell mass across brain structures and species. Graphs show the neuron/glia mass ratio (mnNn/mgNg) as (A) a function of estimated glial cell mass (mg) and (B) a function of the inverse of measured glial cell density (d−1gmes) in each brain structure in each species. Average glial cell mass in picograms; d−1gmes in picograms/neuron. Functions plotted are (A)mn.Nn/mg.Ng = 0.064mg2.433 ± 0.260 (r2 = 0.528, p < 0.0001) and (B)mn.Nn/mg.Ng = 0.132 dgmes−11.072 ± 0.034 (r2 = 0.926, p < 0.0001). Cerebral cortex plotted as circles, cerebellum as squares, and rest of brain as triangles; eulipotyphlans shown in orange, primates in red, and rodents in green. Data from Herculano-Houzel et al. (2006, 2007, 2011), Azevedo et al. (2009), Sarko et al. (2009), and Gabi et al. (2010).

Mentions: Here we find, however, that albeit varying little, as proposed in our previous model, glial cells do not have invariant mass; as shown above, variations in the average mass of glial cells in the tissue are consequent enough to actually impact on the glial mass fraction in the tissue. Once variations in mg are factored in, an even tighter relationship is found in how total glial cell mass, Mg = mg.Ng, varies together with total neuronal mass in the structures, Mn = mn.Nn in strictly the same fashion across all structures and species, in a way that can be described as Mg = 3.078 Mn0.911 ± 0.019 (r2 = 0.968, p < 0.0001; Figure 12E). This implies that the total glial mass in a structure, Mg = mg.Ng, is added in a similar way to all brain structures in all species that matches precisely the total neuronal mass in that structure at a certain ratio: To every certain amount neuronal mass corresponds a certain amount of glial mass in a predictable manner. This is supported by an even better relationship between Ng and the ratio mn.Nn/mg, with Ng = 2.603 (mn.Nn/mg)0.913 ± 0.020 (r2 = 0.965, p < 0.0001; Figure 12D), which suggests that numbers of glial cells are added to match the total neuronal mass in the tissue, but in a way that depends on the precise average mass of the glial cells. Indeed, the ratio Ng/Nn, which we found to vary as a function of mn, is an even better function of the ratio mn/mg, with Ng/Nn = 0.487(mn/mg)0.977 ± 0.030 (r2 = 0.929, p < 0.0001; Figure 11E). The ratio between total neuronal mass and total glial mass, mn.Nn/mg.Ng, which is related (but not identical) to fn, varies between 1 and 3 as mg increases, such that mn.Nn/mg.Ng = 0.064 mg2.433 ± 0.260 (r2 = 0.528, p < 0.0001; Figure 13A), and even more tightly with measured glial cell density in the tissue, such that mn.Nn/mg.Ng = 0.132 d−1gmes1.072 ± 0.034 (r2 = 0.926, p < 0.0001; Figure 13B).


All brains are made of this: a fundamental building block of brain matter with matching neuronal and glial masses.

Mota B, Herculano-Houzel S - Front Neuroanat (2014)

Neuron/glia mass ratio varies with average glial cell mass across brain structures and species. Graphs show the neuron/glia mass ratio (mnNn/mgNg) as (A) a function of estimated glial cell mass (mg) and (B) a function of the inverse of measured glial cell density (d−1gmes) in each brain structure in each species. Average glial cell mass in picograms; d−1gmes in picograms/neuron. Functions plotted are (A)mn.Nn/mg.Ng = 0.064mg2.433 ± 0.260 (r2 = 0.528, p < 0.0001) and (B)mn.Nn/mg.Ng = 0.132 dgmes−11.072 ± 0.034 (r2 = 0.926, p < 0.0001). Cerebral cortex plotted as circles, cerebellum as squares, and rest of brain as triangles; eulipotyphlans shown in orange, primates in red, and rodents in green. Data from Herculano-Houzel et al. (2006, 2007, 2011), Azevedo et al. (2009), Sarko et al. (2009), and Gabi et al. (2010).
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Related In: Results  -  Collection

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Figure 13: Neuron/glia mass ratio varies with average glial cell mass across brain structures and species. Graphs show the neuron/glia mass ratio (mnNn/mgNg) as (A) a function of estimated glial cell mass (mg) and (B) a function of the inverse of measured glial cell density (d−1gmes) in each brain structure in each species. Average glial cell mass in picograms; d−1gmes in picograms/neuron. Functions plotted are (A)mn.Nn/mg.Ng = 0.064mg2.433 ± 0.260 (r2 = 0.528, p < 0.0001) and (B)mn.Nn/mg.Ng = 0.132 dgmes−11.072 ± 0.034 (r2 = 0.926, p < 0.0001). Cerebral cortex plotted as circles, cerebellum as squares, and rest of brain as triangles; eulipotyphlans shown in orange, primates in red, and rodents in green. Data from Herculano-Houzel et al. (2006, 2007, 2011), Azevedo et al. (2009), Sarko et al. (2009), and Gabi et al. (2010).
Mentions: Here we find, however, that albeit varying little, as proposed in our previous model, glial cells do not have invariant mass; as shown above, variations in the average mass of glial cells in the tissue are consequent enough to actually impact on the glial mass fraction in the tissue. Once variations in mg are factored in, an even tighter relationship is found in how total glial cell mass, Mg = mg.Ng, varies together with total neuronal mass in the structures, Mn = mn.Nn in strictly the same fashion across all structures and species, in a way that can be described as Mg = 3.078 Mn0.911 ± 0.019 (r2 = 0.968, p < 0.0001; Figure 12E). This implies that the total glial mass in a structure, Mg = mg.Ng, is added in a similar way to all brain structures in all species that matches precisely the total neuronal mass in that structure at a certain ratio: To every certain amount neuronal mass corresponds a certain amount of glial mass in a predictable manner. This is supported by an even better relationship between Ng and the ratio mn.Nn/mg, with Ng = 2.603 (mn.Nn/mg)0.913 ± 0.020 (r2 = 0.965, p < 0.0001; Figure 12D), which suggests that numbers of glial cells are added to match the total neuronal mass in the tissue, but in a way that depends on the precise average mass of the glial cells. Indeed, the ratio Ng/Nn, which we found to vary as a function of mn, is an even better function of the ratio mn/mg, with Ng/Nn = 0.487(mn/mg)0.977 ± 0.030 (r2 = 0.929, p < 0.0001; Figure 11E). The ratio between total neuronal mass and total glial mass, mn.Nn/mg.Ng, which is related (but not identical) to fn, varies between 1 and 3 as mg increases, such that mn.Nn/mg.Ng = 0.064 mg2.433 ± 0.260 (r2 = 0.528, p < 0.0001; Figure 13A), and even more tightly with measured glial cell density in the tissue, such that mn.Nn/mg.Ng = 0.132 d−1gmes1.072 ± 0.034 (r2 = 0.926, p < 0.0001; Figure 13B).

Bottom Line: We propose that there is a fundamental building block of brain tissue: the glial mass that accompanies a unit of neuronal mass.We argue that the scaling of this glial mass is a consequence of a universal mechanism whereby numbers of glial cells are added to the neuronal parenchyma during development, irrespective of whether the neurons composing it are large or small, but depending on the average mass of the glial cells being added.We also show how evolutionary variations in neuronal cell mass, glial cell mass and number of neurons suffice to determine the most basic characteristics of brain structures, such as mass, glia/neuron ratio, neuron/glia mass ratio, and cell densities.

View Article: PubMed Central - PubMed

Affiliation: Instituto de Física, Universidade Federal do Rio de Janeiro Rio de Janeiro, Brazil ; Instituto Nacional de Neurociência Translacional São Paulo, Brazil.

ABSTRACT
How does the size of the glial and neuronal cells that compose brain tissue vary across brain structures and species? Our previous studies indicate that average neuronal size is highly variable, while average glial cell size is more constant. Measuring whole cell sizes in vivo, however, is a daunting task. Here we use chi-square minimization of the relationship between measured neuronal and glial cell densities in the cerebral cortex, cerebellum, and rest of brain in 27 mammalian species to model neuronal and glial cell mass, as well as the neuronal mass fraction of the tissue (the fraction of tissue mass composed by neurons). Our model shows that while average neuronal cell mass varies by over 500-fold across brain structures and species, average glial cell mass varies only 1.4-fold. Neuronal mass fraction varies typically between 0.6 and 0.8 in all structures. Remarkably, we show that two fundamental, universal relationships apply across all brain structures and species: (1) the glia/neuron ratio varies with the total neuronal mass in the tissue (which in turn depends on variations in average neuronal cell mass), and (2) the neuronal mass per glial cell, and with it the neuronal mass fraction and neuron/glia mass ratio, varies with average glial cell mass in the tissue. We propose that there is a fundamental building block of brain tissue: the glial mass that accompanies a unit of neuronal mass. We argue that the scaling of this glial mass is a consequence of a universal mechanism whereby numbers of glial cells are added to the neuronal parenchyma during development, irrespective of whether the neurons composing it are large or small, but depending on the average mass of the glial cells being added. We also show how evolutionary variations in neuronal cell mass, glial cell mass and number of neurons suffice to determine the most basic characteristics of brain structures, such as mass, glia/neuron ratio, neuron/glia mass ratio, and cell densities.

No MeSH data available.