Brain architecture more complex than previously thought

UK researchers have discovered that cells in the cerebral cortex of mice, called astrocytes, are more diverse than previously thought, with distinct layers of astrocytes across the cerebral cortex that provide the strongest evidence to date of their specialisation across the brain. Published in the journal Nature Neuroscience, the study will have implications for the study of neurological disorders such as Alzheimer’s, multiple sclerosis and autism.

In the past 20 years, research has shown glial cells (of which astrocytes are one subtype) to be key players in brain development and function, as well as promising targets for better understanding neurological disorders. At one time, glial cells were thought of as ‘brain putty’ — functionally similar, passive cells whose only function was to fill the space around the all-important neurons. However, new studies are showing their critical importance in regulating neuron functions.

Despite the wealth of knowledge on neuronal function and the organisation of neurons into layers, prior to this study there had been little investigation into whether glial cells across different layers showed different cellular properties. To answer this question, the researchers developed a new methodological approach to provide a more detailed view of the organisation of astrocytes than ever before.

Nucleic acid imaging was carried out on mouse and human brain samples at the University of Cambridge to map how new genes are expressed within tissue. These maps were combined with single-cell genomic data at the Wellcome Sanger Institute to extend the molecular description of astrocytes. These datasets were then combined to create a three-dimensional, high-resolution picture of astrocytes in the cerebral cortex.

The team discovered that astrocytes are not uniform as previously thought, but take distinct molecular forms depending on their location in the cerebral cortex. They found that astrocytes are also organised into multiple layers, but that the boundaries of astrocyte layers are not identical to the neuronal layers. Instead, astrocyte layers have less sharply defined edges and overlap the neuronal layers.

“The discovery that astrocytes are organised into layers that are similar, but not identical to, neuronal layers redefines our view of the structure of the mammalian brain,” said Dr Omer Bayraktar, Group Leader at the Wellcome Sanger Institute. “The structure of the cerebral cortex can no longer simply be seen as the structure of neurons. If you want to properly understand how our brains work, you have to consider how astrocytes are organised and what role they play.”

As well as increasing our understanding of brain biology, the findings will have implications for the study and treatment of human neurological disorders. Over the past decade glial cells, rather than neurons, have been heavily implicated in diseases such as Alzheimer’s and multiple sclerosis.

“This study shows that the cortical architecture is more complex than previously thought,” said Professor David Rowitch, Head of Paediatrics at the University of Cambridge. “It provides a basis to begin to understand the precise roles played by astrocytes, and how they are involved in human neurodevelopmental and neurodegenerative diseases.”

Image credit: ©stock.adobe.com/au/Tiko

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