Many details of living human brain tissue have been catalogued.
Fresh human brain tissue is a vanishingly rare resource for neuroscientists, not least because it is invaluable to its original owner. Yet sometimes patients will surrender a sugar-cube sized chunk of brain when undergoing surgery to remove a tumour or to treat severe epilepsy. On 25 October researchers at the Allen Institute for Brain Science in Seattle, USA, who compile large-scale databases, brain maps and other tools for neuroscience research, announced that they had put their first batch of data from live human brain cells into a publically available database.
Most human brain studies use either images of functioning brains obtained by scanning volunteers or slices of dead organs obtained from cadavers. The database created by the Allen Institute uses living brain cells or neurons, which enables researchers to image and analyse the molecular content of individual cells and, ultimately, to identify the biological basis of their behaviour. However until now, the database has only contained information about mouse brains.
The publication of human data represents the latest – and most extensive and systematic – step in the ongoing efforts to identify the uniqueness of the human brain since such work tentatively began in the 1970s.
Neurosurgeons in the Seattle region donated, with the consent of patients, small pieces of brain that they would otherwise have discarded during surgery: bits of the outer layer called the cortex that they needed to snip out in order to access diseased tissue deeper in the brains of their patients.
The cortex processes higher-level activities, including the deep introspection and abstract reasoning that is thought to be uniquely human. “Finding out what the detailed differences are between the mouse and human brain will help us understand what makes us unique among species,” says Christof Koch, president and chief scientific officer of the institute.
The first slew of human data includes the electrical properties of 300 different types of neuron from 36 patients, along with 3-D reconstructions of the spidery shapes of some of them, and computer models that simulate their electrical behaviour. It also includes profiles of gene expression of 16,000 individual cells from the brains of another three patients. Scientists around the world may now compare these data with mouse data to generate hypotheses about where key differences lie.
“This database is a major service to the scientific community,” says Huib Mansvelder from the University of Amsterdam, an early pioneer of research on fresh human brain cells. He has shown, for example, that human neurons have a lower capacitance than mouse neurons, which makes them quicker to start firing and quicker transfer information. They also have more intricate shapes . “But the Allen’s industrial approach takes the endeavour to a whole new level,” he says.
A sugar-lump size of donated tissue from a patient’s brain is typically the same volume as an entire mouse brain. Cut into slices 300-350 micrometres thick, its cells remain alive and active for at three days, giving scientists ample time to make their measurements. Mouse neurons, by contrast, tend to degenerate within hours.
Only a few research centres worldwide work with fresh human brain tissue, partly because until recently not many brain surgeons have wanted to work with them. But rapid developments in biological research tools and have made donation more useful.
The Allen Institute now plans to extend the number of human brain cells in its database and will also increase the amount of information from each of them, aiming to include full RNA profiles to indicate which genes are active. A next phase will also analyse the connections between the cells. However the work will necessarily lack the comprehensiveness of the study of mouse brains, because only small pieces of living human brains can be removed, whereas the whole brains of mice can be studied.
Many scientists have worried that gaining fresh tissue from diseased brains could be problematic. The apparently healthy tissue comes from a brain with a disease, which provokes concerns that its properties may have been altered by its pathological environment. However Mansvelder has compared cortical tissue from patients with cancer or epilepsy and found them very similar. The Allen Institute has now confirmed these results.
There is another advantage to using human cortical tissue. Neurosurgical teams collect vast information about the brain functions of their patients before and after surgery which can, with appropriate anonymization, be correlated with cellular properties. At a meeting of the Federation of European Neuroscience Societies in Pecs, Hungary, held on 20-23 September, Mansvelder presented data showing that IQ correlated with the threshold of firing of cells – the higher the IQ, the lower the threshold.
Mansvelder, along with another pioneer, Gabor Tamas from the University of Szeged, Hungary, and groups from Israel and Sweden, will collaborate with the Allen Institute to develop the human brain database further, thanks to a US$19.4 million international grant from the Bethesda-based National Institutes of Health, announced on 23 October.
 Eyal, G. et al. (2016) eLife. E165553
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Abbott, A. Researchers add live human cells to brain database. Nature (2017). https://doi.org/10.1038/nature.2017.22889