Fluorescent biosensors deliver insights into brain activity

Thanks to a new method developed at the University of Zurich (UZH), researchers can now observe for the first time in a living brain how neuropeptides – also known as signaling molecules or neurotransmitters – contribute to healthy brain function. Up to this point, there have been no instruments that provide spatial and temporal resolution. Now the research group can investigate one of the most pressing questions in neurophysiology: just how does the signaling molecule system orexin work?

Orexin regulates arousal, wakefulness, motivation and appetite. According to UZH, a defect in the release or sensing of orexin neuropeptides can cause narcolepsy both in humans and animals. Those affected by this condition suffer from overwhelming and uncontrollable daytime drowsiness.

In order to investigate the relationship between neuronal activity and orexin release in living animals when running or during periods of acute stress – and, crucially, to make this visible under the microscope – Tommaso Patriarchi from the Institute of Pharmacology and Toxicology at UZH developed a genetically encoded biosensor with fluorescent properties, further details of which can be found in a press release issued by the university. This new orexin biosensor by the name of OxLight1 is integrated in the human orexin receptor. “When the neuropeptide binds to the receptor, it makes it light up”, says Patriarchi in explaining the method.

“After deciphering orexin release and neuronal activity in the healthy brain, we are now using OxLight1 to investigate the mechanisms of brain diseases like narcolepsy and addiction”, Patriarchi explains further. For this, he received financial support in the form of an ERC Starting Grant from the European Research Council. According to UZH, the biosensors developed by his team are already being used in laboratories around the world. Now the focus will be on continuing to expand the neuro-technological toolbox with the aim of establishing new screening tests for drug development activities.