In an article in the cell, researchers funded by the National Institutes of Health described how they used advanced genetic engineering techniques to transform bacterial proteins into a new research tool that serotonin transmission with greater fidelity than current methods May help in monitoring.
Preclinical experiments primarily in mice showed that the sensor could detect subtle, real-time changes in brain serotonin levels during sleep, fear, and social interactions, as well as testing the effectiveness of new psychoactive drugs. .
The study was funded by Brain Research of NHH through the Advancing Innovative Neurotechnology (BRIN) initiative, which aims to revolutionize our understanding of the brain in healthy and pathological conditions.
The study was led by researchers in the laboratory of University of California Davis School of Medicine chief investigator Lin Tian. Current methods can only detect widespread changes in serotonin signaling. In this study, researchers transformed a nutrient-grabbing, Venus flytrap-shaped bacterial protein into a hyper-sensitive sensor that fluoresces lightly when capturing serotonin.
Earlier, Lauren L. Logar, PhD, scientists at the Lab of the Howard Hughes Medical Institute Genelia Research Campus, Ashburn, Virginia, have converted bacterial proteins into sensors of the neurotransmitter acetylcholine using traditional genetic engineering techniques.
A protein, called opuBC, usually snags the nutrient choline, which has the same size as acetylcholine. For this study, Tian Lab provided Drs. Loegher’s team and Viviana Gradinaru, PhD, worked with the laboratory of Caltech, Pasadena, California, to show that they needed the additional help of artificial intelligence to make OpuBC completely new as a serotonin catcher.
Researchers used machine learning algorithms to help the computer “think”, with 250,000 new designs. After three rounds of testing, the scientists settled on one. Initial experiments suggested that the new sensor detected serotonin at different levels in the brain while there was no response to other neurotransmitters or drugs of similar size.
Experiments in mouse brain slices showed that the sensor responded to serotonin signals sent between neurons at synaptic communication points. Meanwhile, experiments on cells in a petri dish suggested that the sensor could monitor changes in these signals caused by drugs, including cocaine, MDMA (also known as ecstasy), and many commonly used antidepressants. is.
Finally, experiments in mice showed that the sensor could help scientists study serotonin neurotransmission under more natural conditions. For example, researchers observed that serotonin levels increased when mice were awake and slept as mice.
When the mice finally entered deep, REM sleep, they were shown to decline more. Traditional serotonin monitoring methods may have missed these changes. In addition, scientists observed that serotonin levels differ in two different brain fear circuits, when mice were warned of a foot tremor by the ringing bell.
In one circuit – the medial prefrontal cortex – there is a rapid and high increase in serotonin levels from the bell while in another – the basolateral amygdala – the transmitter rises to slightly lower levels.
In the spirit of the Bryan initiative, researchers plan to make the sensor readily available to other scientists. They hope this will help researchers gain a better understanding of the role serotonin plays in our daily lives and in many psychiatric conditions.