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In an article in Cell, researchers funded by the National Institutes of Health described how they used advanced genetic engineering techniques to turn a bacterial protein into a new research tool that can help monitor the transmission of serotonin with greater high fidelity than current methods.
Preclinical experiments, primarily in mice, have shown that the sensor can detect subtle, real-time changes in brain serotonin levels during sleep, fear, and social interactions, as well as test the effectiveness of new psychoactive drugs.
The study was funded, in part, by NIH’s Brain Research through Advancing Innovative Neurotechnologies (BRAIN) initiative, which aims to revolutionize our understanding of the brain under healthy and pathological conditions.
The study was conducted by researchers in the lab of Lin Tian, Ph.D, a senior researcher at Davis School of Medicine at the University of California. Current methods can only detect significant changes in serotonin signaling. In this study, the researchers transformed a bacterial protein in the form of a Venus fly trap that captures nutrients into a very sensitive sensor that fluoresces when it captures serotonin.
Previously, scientists at the laboratory of Loren L. Looger, Ph.D, Howard Hughes Medical Institute Janelia Research Campus, Ashburn, Virginia, used traditional genetic engineering techniques to convert the bacterial protein into a sensor for the neurotransmitter acetylcholine.
The protein, called OpuBC, normally binds nutrient choline, which is similar in shape to acetylcholine. For this study, the Tian Lab worked with Dr. Looger’s team and the lab of Viviana Gradinaru, Ph.D, Caltech, Pasadena, Calif., To show they needed the extra help of artificial intelligence. to completely rethink OpuBC as a serotonin sensor.
The researchers used machine learning algorithms to help a computer “imagine” 250,000 new models. After three rounds of tests, the scientists opted for one. Early experiments suggested that the new sensor reliably detected serotonin at different levels in the brain while having little or no response to other neurotransmitters or drugs of similar form.
Experiments on mouse brain sections showed that the sensor responded to serotonin signals sent between neurons at synaptic communication points. Meanwhile, experiments on cells in Petri dishes suggested that the sensor could effectively monitor changes in these signals caused by drugs, including cocaine, MDMA (also known as ecstasy) and several commonly used antidepressants.
Finally, experiments in mice have shown that the sensor can help scientists study the neurotransmission of serotonin under more natural conditions. For example, researchers saw an expected increase in serotonin levels when mice were awake and a drop when mice fell asleep.
They also spotted a larger drop when the mice finally entered states of deeper REM sleep. Traditional methods of serotonin monitoring would have missed these changes. Additionally, scientists saw serotonin levels rise differently in two separate brain fear circuits when mice were warned of a foot shock by a ringing bell.
In one circuit – the median prefrontal cortex – the bell triggered a rapid and elevated rise in serotonin levels while in the other – the basolateral amygdala – the transmitter crawled to slightly lower levels.
In the spirit of the BRAIN initiative, the researchers plan to make the sensor easily accessible to other scientists. They hope this will help researchers better understand the critical role of serotonin in our daily lives and in many psychiatric conditions.
(This article was posted from an agency feed with no text changes. Only the title has been changed.)
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