Light-sensitive serotonin receptors may help study causes of anxiety, depression

Apr 26 2016

Anxiety and depression are two of the most frequently occurring mental disorders worldwide. Light-activated nerve cells may indicate how they are formed.

By coupling nerve cell receptors to light-sensitive retinal pigments, Prof Dr Olivia Masseck researches into the causes of anxiety and depression. For more than 60 years, researchers have been hypothesising that the diseases are caused by, among other factors, changes to the level of the neurotransmitter. "Unfortunately, it is very difficult to understand how the serotonin system works," says Masseck, who became junior professor for Super-Resolution Fluorescence Microscopy at the Ruhr-Universität Bochum (RUB) in April 2016.

Complex serotonin system

The number of receptors for the neurotransmitter in the brain amounts to 14, occurring in different cell types. Consequently, determining the functions that different receptors fulfil in the individual cell types is a complicated task. If, however, the proteins are coupled to light-sensitive pigments, they can be switched on and off with light of a specific colour at high spatial and temporal precision.

The RUB's science magazine Rubin has published a report on how Olivia Masseck uses this method, i.e. optogenetics. She characterises, for example, the properties of different light-sensitive proteins and identifies the ones that are best suited as optogenetic tools. She has analysed several light-sensitive varieties of the serotonin receptors 5-HT_1A and 5-HT_2C in great detail. Together with her cooperation partners, she has demonstrated in several studies that both receptors can control the anxiety behaviour of mice.

Real-time serotonin sensor planned

In order to investigate the serotonin system more closely, the researcher is currently developing a sensor that is going to indicate the neurotransmitter in real time. One potential approach involves the integration of a modified form of a green fluorescent protein into a serotonin receptor.

This protein produces green light only if it is embedded in a specific spatial structure. If a serotonin molecule binds to a receptor, the receptor changes its three-dimensional conformation. The objective is to integrate the fluorescent protein in the receptor so that its spatial structure changes together with that of the receptor when it binds a serotonin molecule - in such a way that the protein begins to glow.