Decoding lateral habenular neuromodulation: Development of a red serotonin sensor for multiplex in vivo imaging of serotonin and noradrenaline

• Applicant: Professorin Dr. Olivia Andrea Masseck
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 573268786

We aim to advance the understanding of neuromodulatory signaling in the lateral habenula (LHb) by developing and applying novel tools for real-time in vivo imaging of serotonin (5-HT) and norepinephrine (NE). As a first step, we will optimize the mScarlet-based serotonin sensor sParken through linker engineering and site-directed mutagenesis, followed by high-throughput screening and in vitro validation. The improved sensor will be benchmarked against established indicators and validated for in vivo use via fiber photometry during optogenetically evoked 5-HT release. Second we will combine sParken with the green NE sensor nLightG2.0 to enable dual-color fiber photometry in the LHb of mice performing a standardized decision-making task. This approach will allow us to track NE and 5-HT dynamics during learning, reversal, and behavioral adaptation.Together, this project combines tool development with systems-level behavioral neuroscience to enable multiplex neuromodulator imaging and provide new mechanistic insight into LHb function in value-based decision-making.

• DFG Programme: Research Grants