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Living brain donors help better understand neurons

7 October 2021
An international team of neuroscientists worked on a study of living neurons from brain tissue donated by patients from neurosurgical operations to treat epilepsy or brain tumours. VU scientist Huib Mansvelder and his team have also contributed to this with neurosurgeons from the VUmc.

The study is part of a series of studies by international consortia brought together by the National Institutes of Health’s BRAIN Initiative, published this week in the journal Nature. The goal of this large research programme, worth more than 4 billion dollars, is to map all brain cells of different mammal species, rodents, monkeys and humans.

Among other things, scientists in the consortium built a very detailed map of the motor cortex. It forms the basis for the entire brain inventory and is by far the most comprehensive and detailed map of the mammalian brain ever made. Developing a better understanding of the brain's "parts-list" is a critical step toward understanding the brain as a whole. It also provides more insight into brain diseases, such as ALS.

New technology
To typify brain cells, the molecular signature of gene expression was determined for each cell individually. The human brain contains about 86 billion nerve cells and to determine the expression of ten thousand genes or more from each cell individually, new technologies are needed. “The cell is the basic unit of life. A major effort through the history of neuroscience has been trying to define the types of cells that make up the brain,” said Ed Lein, Senior Investigator at the Allen Institute for Brain Science, who led the study.

Living neurons
The study to which Mansvelder and team contributed goes a step further, namely by studying the consequences of gene expression for cell shape and function of the mapped cell types. Mansvelder: “We find that these evolutionarily developed parts of the human brain contain cell types that cannot be seen in mice. The increased molecular diversity in humans is reflected in the diversity in the shape and function of the cells. The more 'human-specific' brain cell types are among the first to disappear in Alzheimer's disease."

Studying human brain cells in living human brain tissue is only done in a limited number of places in the world. It requires close collaboration between fundamental neuroscientists and the neurosurgery department, where surgical treatment of epilepsy and tumour patients takes place. In order to study sufficient brain material for the research, the laboratories from the different countries took part.

The studies are financed by the US Brain Initiative Cell Census Network programme. The study in which Mansvelder and his team are involved was co-financed by the NWO Gravity programme 'Brainscapes' of VU and the European Human Brain Project.