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Serotonergic neurons project to most regions of the brain and serotonin is a modulatory neurotransmitter that control many neurocircuitries. Release and reuptake of serotonin in the brain is at the heart of many natural behavioral responses, drug actions and psychiatric disease states, e.g. depression. However, serotonin dynamics is difficult to study with the resolution in space and time needed to learn more about the brain and its disorders.

Genetically encoded fluorescent biosensors have revolutionized the study of the brain because they allow us to monitor changes in e.g. neurotransmitter levels in the milisecond domain with cellular resolution in the brain of freely moving, unanesthetized animals engaging in complex behaviors and/or exhibiting models of psychiatric disorders.We will engineer a genetically encoded biosensor for the determination of absolute levels of serotonin in vivo and vitro. 

The biosensor will be based on our succesful previous development of a genetically encoded biosensor for serotonin that utilized fluorescent intensity (FI) changes, but the new biosensor will benefit from fluorescent lifetime (FL) as the readout mode.The advantages of biosensors using FL instead of FI are substantial because it opens the door to much more advanced and more disease-related studies. Most importantly, FL allows the absolute, quantitative measurement of neurotransmitter concentrations rather than just relative changes as reported by FI biosensors. FL is independent of environmental factors that negatively impact FI. FL is also independent of a number of confounding technical limitations encountered in complex biological environments.

These advantages means that FL, in contrast to FI, allows longitudinal studies and easier comparison between animals, which is crucial to understand the neurochemistry and neurobiology in preclinical animal models of psychiatric disorders, where both the development of the disease and its cure usually takes weeks or months.