Serotonin is a neurochemical that plays an essential role in the manner the brain controls our thoughts and feelings. For instance, most antidepressants are designed to modify the serotonin signals sent between neurons. In an article in Cell, National Institutes of Health-funded researchers explained how they made use of advanced genetic engineering techniques to convert a bacterial protein into a novel research tool that may aid the supervision of serotonin transmission with greater dedication than present methods.
Preclinical experiments, mostly in mice, illustrated that the sensor could identify subtle, real-time changes in brain serotonin levels during sleep, fear and social interactions and also test how effective the new psychoactive drugs are.
The study was funded partly by the NIH’s Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative whose aim is to revolutionize our comprehension of the brain under healthy and disease conditions.
Researchers in the lab of Lin Tian, Ph.D., Principal Investigator at the University of California Davis School of Medicine led this study. Present methods can only locate large changes in serotonin signaling. In this study, the researchers converted a nutrient-grabbing bacterial protein shaped like a Venus flytrap into a very sensitive sensor that lights up when it catches serotonin,
Previously, scientists in the lab of Loren L. Looger, Ph.D., Howard Hughes Medical Institute Janelia Research Campus, Ashburn, Virginia, made use of customary genetic engineering methods to transform the bacterial protein into a sensor of the neurotransmitter acetylcholine.
The protein called OpuBC normally catches the nutrient choline which is similar shaped to acetylcholine. For this study, the Tian lab worked with Dr. Looger’s team and the lab of Viviana Gradinaru, Ph.D., Caltech, Pasadena, California to prove they required the advanced assistance of artificial intelligence to completely redesign the OpuBC as a catcher for serotonin.
The researchers made use of machine learning algorithms to aid the computer ‘think up’ 250,000 new designs. After three rounds of testing, the scientists decided on one. The earliest experiments suggested that the new sensor reliably identified serotonin at various levels in the brain while having almost no reaction to other neurotransmitters or drugs with similar shapes.
The experiments on the mouse brain slices showed that the sensor reacted to serotonin signals sent between neurons at synaptic communication points.
Meanwhile, experiments done on cells in petri dishes suggested that the sensor could effectively oversee the alterations in the signals caused by drugs, including cocaine, MDMA (ecstasy) and other commonly used antidepressants.
Finally, the experiments done on mice showed that the sensor could help scientists examine serotonin neurotransmission under more natural conditions. For example, the researchers observed a foreseen increase in serotonin levels when the mice were conscious and a fall when they were asleep. They also witnessed a greater drop when the mice entered the deeper R.E.M. sleep state.
Customary serotonin monitoring techniques wouldn’t have been able to spot these changes. Additionally, the scientists observed the serotonin levels rise differently in two separate brain fear circuits when the mice were alerted of a foot shock by a ringing bell.
In one circuit― the medial prefrontal cortex― the bell made the serotonin levels rise fast. In the other― the basolateral amygdala― the transmitter crawled to slightly lower levels.
In the spirit of the BRAIN initiative, the plan of the researchers is to make the sensor accessible to other scientists.
They hope it will help researchers comprehend better, the important role serotonin plays in our lives and in many psychiatric conditions.
By Marvellous Iwendi
Source: NIH