Published: 2015-12-21 17:10 | Updated: 2016-01-21 10:55

Potent combination of two methods reveals neuronal identity

In two separate studies published in the same issue of the journal Nature Biotechnology, researchers at Karolinska Institutet and their Austrian and American colleagues have managed to combine two methods of potentially analysing and mapping all the brain’s cell types at single-cell level. The new ‘Patch-seq’ combination method makes it possible for scientists to identify new and previously unknown neuronal types in the brain and to gain an understanding of their particular function in relation to specific behaviours.

The first study was a collaboration between Rickard Sandberg, professor at Karolinska Institutet’s Department of Cell and Molecular Biology and also affiliated to the Ludwig Cancer Research, and Dr Andreas Tolias at Baylor College of Medicine, USA. The second study was a collaboration between Sten Linnarsson, professor at Karolinska Institutet’s Department of Medical Biochemistry and Biophysics, and Tibor Harkany, professor at the same department, and also at MedUni Vienna in Austria. Previous studies, in which the more recent of the two techniques was presented, have been published in several journals, including Science and Nature Methods.

In these two new studies in Nature Biothechnology, the researchers have managed for the first time to bring the two methods together into a novel combination. The first method is electrophysiology, a classic technique that has long been the standard means of classifying nerve cells in the brain and that involves the insertion of a very narrow pipette into individual nerve cells for the purpose of measuring their electrical properties. The second method is single-cell RNA sequencing, which allows scientists to measure which genes are active in a specific cell, and thus determine its molecular identity. In the present studies, the researchers took the electrophysiological measurements of a single cell before sucking out its entire contents through the pipette in order to analyse which genes are active in that particular cell.

Valuable to brain research

“The combination method can prove very valuable to brain research,” says Professor Linnarsson. “The method allows us to find out which cells communicate with each other in the neural networks of the brain by taking electrophysiological measurements, and which cell types make up these networks.”

Another possible area of application is the study of brain diseases where information is available on which genes are involved. The combination of techniques also makes it possible to link the genetic and electrophysiological properties of single cells to better understand the types of cell that are involved in different disorders.

The two studies were conducted independently of each other and financed with grants from several sources, including the Swedish Research Council, the Swedish Foundation for Strategic Research, the European Research Council, the EU’s Seventh Framework Programme and the Swedish Brain Fund.

Text: Karin Söderlund Leifler (in translation from Swedish)


Morphological, electrophysiological and transcriptomic profiling of single neurons using Patch-seq’, Cathryn R. Cadwell , Athanasia Palasantza, Xiaolong Jiang, Philipp Berens1, Qiaolin Deng, Marlene Yilmaz, Jacob Reimer, Shan Shen, Matthias Bethge, Kimberley F. Tolias, Rickard Sandberg, and Andreas S. Tolias, Nature Biotechnology, online 21 December 2015, doi: 10.1038/nbt.3445.

Integration of electrophysiological recordings with single-cell RNA-seq data identifies neuronal subtypes’, Janos Fuzik, Amit Zeisel, Zoltán Máté, Daniela Calvigioni, Yuchio Yanagawa, Gábor Szabó, Sten Linnarsson, and Tibor Harkany, Nature Biotechnology, online 21 December 2015, doi: 10.1038/nbt.3443.