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A new study reveals surprising spatial organisation of 'star-shaped' cells in the mammalian brain.

The mammalian brain remains a puzzle-box for scientists, who continue to struggle in unlocking its secrets. From the intricacies of its higher processing, to the fundamentals of its architecture, it is clear that the structure is extremely complex and remains confusing to understand. However, contemporary research continues to illuminate key features of the brain that help build a general picture of the organ, and may also help us treat neurological disorders. A new study on mouse and human brains does just that: by using molecular biology techniques in a high-throughput analysis pipeline, Omar Bayraktar and colleagues reveal novel insights into the spatial organisation of the mammalian brain.

The research, published in Nature Neuroscience on 16 March, focuses on a type of cell in the brain called an ‘astrocyte’, so-named for its star-like shape. It is well known that the brain is composed of neurons: nerve cells that transmit information across the body and therefore are critical in coordinating physiological function. However, the brain is also composed of glial cells, of which astrocytes are the most abundant type; glial cells make up approximately 50% of the brain’s total cell count. ‘Glia’ is the Greek for ‘glue’, and it was originally thought that these cells were simply involved in providing structural and homeostatic support for the all-important neurons, and thus are largely homogeneous in the brain. However, recent insights – such as this research from the Rowitz lab in Cambridge – have begun to reveal that these cells may be doing much more than originally thought.

The new study reveals that astrocytes have a spatial organisation, which suggests that they may have a wider functional role than just as ‘brain glue’. The authors characterise the organisation of the brain through an automated analysis pipeline: the LaST map (Large area Spatial Transcriptomic map). In this pipeline, brain sections are scanned for their ribonucleic acid and protein content. By dividing the brain into regions dependent on their nucleic acid and protein content, it is possible to build a characterised map of the brain. The results from the LaST scan on mouse brain samples were used to build a picture of astrocyte organisation, before being confirmed by other techniques to sample nucleic acid content, and also compared to human samples run through the pipeline.

Interestingly, the study shows that astrocytes in the mammalian brain have a somewhat different organisation than neurons. Neurons in the grey matter of the brain’s cerebral cortex – responsible for higher order processing – are classically divided into six layers in the mammalian brain, and this neuronal layering was also seen on the map defined by Bayraktar and colleagues. In the study, astrocytes were also seen to be layered in the mouse cortex, but instead divided into three layers (called superficial, mid and deep). While overlapping, these astrocyte layers did not correspond to neuronal layers.

The implication of this study is to reinforce the emerging view that glial cells are more than just neuronal support: their spatial organisation suggests a wider function, and critically their distinct layering from neurons suggests that this function may be fairly independent. However, a clear picture of what glial cells are doing remains to be found – what function are they serving that requires their unique spatial organisation? Furthermore, it is possible that the development of the different layering patterns is linked, and astrocyte function – while more complex than previously thought – is still largely based on neuronal maintenance.

Understanding glial cells is critical not only in developing a generalised picture of the human brain, but also because these cells have been heavily implicated in neurological disorders. It is known that astrocytes change their reactivity and morphology in cases of major neural diseases such as multiple sclerosis, Parkinson’s Disease, ALS and Alzheimer’s. Whether they have a greater implication on disease than their homeostatic and structural role, remains to be seen.

Publication: Omer Ali Bayraktar, Theresa Bartels, Staffan Holmqvist et al. (2020). Astrocyte layers in the mammalian cerebral cortex revealed by a single-cell in situ transcriptomic map. Nature Neuroscience.

Adiyant Lamba is a news editor at Bluesci