Next generation genetically encoded fluorescent sensors for serotonin

Martin Kubitschke, Monika Müller, Lutz Wallhorn, Mauro Pulin, Manuel Mittag, Stefan Pollok, Tim Ziebarth, Svenja Bremshey, Jill Gerdey, Kristin Carolin Claussen, Kim Renken, Juliana Groß, Pascal Gneiße, Niklas Meyer, J. Simon Wiegert, Andreas Reiner, Martin Fuhrmann and Olivia Andrea Masseck ()
Additional contact information
Martin Kubitschke: University of Bremen
Monika Müller: German Center for Neurodegenerative Diseases (DZNE)
Lutz Wallhorn: University of Bremen
Mauro Pulin: Center for Molecular Neurobiology (ZMNH), UKE
Manuel Mittag: German Center for Neurodegenerative Diseases (DZNE)
Stefan Pollok: Ruhr University Bochum
Tim Ziebarth: Ruhr University Bochum
Svenja Bremshey: University of Bremen
Jill Gerdey: University of Bremen
Kristin Carolin Claussen: University of Bremen
Kim Renken: University of Bremen
Juliana Groß: University of Bremen
Pascal Gneiße: University of Bremen
Niklas Meyer: University of Bremen
J. Simon Wiegert: Center for Molecular Neurobiology (ZMNH), UKE
Andreas Reiner: Ruhr University Bochum
Martin Fuhrmann: German Center for Neurodegenerative Diseases (DZNE)
Olivia Andrea Masseck: University of Bremen

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract We developed a family of genetically encoded serotonin (5-HT) sensors (sDarken) on the basis of the native 5-HT1A receptor and circularly permuted GFP. sDarken 5-HT sensors are bright in the unbound state and diminish their fluorescence upon binding of 5-HT. Sensor variants with different affinities for serotonin were engineered to increase the versatility in imaging of serotonin dynamics. Experiments in vitro and in vivo showed the feasibility of imaging serotonin dynamics with high temporal and spatial resolution. As demonstrated here, the designed sensors show excellent membrane expression, have high specificity and a superior signal-to-noise ratio, detect the endogenous release of serotonin and are suitable for two-photon in vivo imaging.

Date: 2022
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DOI: 10.1038/s41467-022-35200-w

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