In a nutshell: Using a newly developed method, researchers have produced a more accurate record of the number and location of cells in the brain.

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To understand how the structure of the brain is linked to its development and function, researchers need to know how many cells are in each part of the brain. This is important, for example, when creating simulations of brain activity. However, this basic information has been surprisingly difficult to obtain.

A current method, called isotropic fractionation, uses a soup-like mixture of pulverized brain cells to give an approximate number, but in the process it loses information about which parts of the brain contain which cells.

Now, Brain Function CoE investigators Nafiseh Atapour, Piotr Majka and Marcello Rosa, along with colleagues at Monash University, have produced the first complete map of cells in a primate cerebral cortex – the thick outer layer of folded grey matter that covers much of the surface of the brain and is involved in consciousness.

The researchers cut the cerebral cortices from a marmoset monkey vertically into columns measuring 1 square millimetre at their top surface. After staining them to reveal individual brain cells, they took digital images of the columns so they could zoom in and count the cells. A total of 116 structural areas have been defined in the marmoset cortex, so the researchers grouped the columns into these areas to investigate how cell density varies across the brain.

Based on their comprehensive census, the researchers estimate that the marmoset cerebral cortex contains approximately 300 million cells. Cell density varies significantly across the structural areas, with some areas almost four times as dense as others. For example, the primary visual cortex, which processes visual information, has more than 150,000 cells per cubic millimetre of brain – adding up to more than a quarter of the total cells in the marmoset cerebral cortex. By contrast, some allocortical areas – thinner regions of the brain that include the area responsible for processing odour – have only around 50,000 cells per cubic millimetre.

Previously, it was believed that brain areas performing more complicated cognitive tasks would have fewer cells, because more space was needed for the wiring that transmits information between cells. The researchers showed that this was true for some areas, but not others – suggesting that other factors are involved in the relationship between cell density and brain function. They believe that the way different genes are turned on and off in the cells within each cortical area during brain development may help to influence the cell density in those areas.

Next steps:
The researchers plan to look at different subtypes of brain cells to see if and how their number and location vary across the brain. They are also developing automated methods for identifying these subtypes, so that this type of work can be conducted more rapidly in the future.

Atapour, N., Majka, P., Wolkowicz, I. H., Malamanova, D., Worthy, K. H., & Rosa, M. G. P. (2018). Neuronal distribution across the cerebral cortex of the marmoset monkey (Callithrix jacchus). Cerebral Cortex, bhy263. doi: 10.1093/cercor/bhy263

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