A research team from the University of Cologne, together with researcher form the University of Tokio has developed a calcium sensor that can track the activity of nerve cells in the brain more effectively than previous sensors. For the first time, the sensor combines the advantages of red and green calcium sensors: it is significantly brighter than previous red versions and, at the same time, provides deeper insights into the brain. The study ‘PinkyCaMP: an mScarlet-based calcium sensor with enhanced brightness, photostability and multiplexing capabilities’ was published in the journal Nature Methods.
Researchers study the activity of nerve cells in order to understand how the brain processes information. Calcium sensors light up when nerve cells are active, thus allowing neural networks to be observed in real time. Red fluorescent sensors are particularly valuable because they enable imaging deeper inside brain tissue compared toe green sensors and can be combined with other optical techniques. However, until now, such sensors were associated with significant limitations. In addition to their lower level of brightness in comparison with green-fluorescent variants, they are prone to light-induced artefacts, i.e. undesirable changes in fluorescence caused by exposure to light. As a result, modern experimental approaches in particular, such as the combination of optogenetic techniques or multicolour imaging, have been restricted in use.
PinkyCaMP overs comes these challnegs and is the brightest and most photostable red-fluorescent calcium sensor to date. It is significantly brighter than previous red sensors and provides an improved signal-to-noise ratio, a metric for the quality of the measurement signal. This enables reliable measurements even under difficult conditions, and stable long-term recordings of neural activity. At the same time, it does not exhibit any light-induced artefacts caused by exposure to light, which is a decisive advantage for many modern applications. PinkyCaMP is based on the fluorescent protein mScarlet from which it had not previously been possible to develop a biosensor, This makes PinkyCaMP the first successful sensor of its kind.
This sensor opens up new experimental possibilities. It can be combined with optogenetic methods and other fluorescent biosensors, and is suitable for multi-colour experiments. This allows for a better analysis of complex interactions between different cell types and neural networks.
“PinkyCaMP is well tolerated by nerve cells and shows no harmful effects, even over the long term. In this respect, too, the sensor therefore represents a step forward,” says Professor Dr Olivia Masseck from the University of Cologne’s Institute of Zoology, who has led the development of the sensor. “PinkyCaMP is versatile and compatible with a wide range of modern imaging processes, from fibre photometry and miniscope imaging to two-photon microscopy in conscious and unrestrained animals.”
The research was funded by the German Research Foundation (DFG).
Media Contact:
Professor Dr Olivia Masseck
Institute of Zoology
+49 221 470 3119
o.masseck(at)uni-koeln(dot)de
Press and Communications Team:
Jan Voelkel
+49 221 470 2356
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Publication:
https://www.nature.com/articles/s41592-026-03065-2