AL redesigned a bacterial protein that helps researchers track serotonin in the brain

AL redesigned a bacterial protein that helps researchers track serotonin in the brain

AI-Designed Serotonin Sensor will help scientists’ research sleep and mental health. Artificial intelligence technology has redesigned a bacterial protein that lets researchers detect serotonin in the brain in real-time. Serotonin is a neurochemical that plays a vital part in how the brain regulates our emotions and feelings. For eg, several antidepressants are intended to modify the signals of serotonin transmitted between neurons. In a cell study, the National Institutes of Health-funded researchers explained how sophisticated genetic engineering techniques have been used to turn bacterial proteins into a modern research tool that can help control serotonin delivery more faithfully than existing methods.

NIH BRAIN Initiative scientists used machine learning to redesign a bacterial ‘Venus flytrap’ protein that can monitor brain serotonin levels in real-time.

Preclinical studies, mainly in mice, have demonstrated that the sensor can track small, real-time shifts in brain serotonin levels during sleep, anxiety, and social experiences, as well as assess the efficacy of novel psychoactive drugs. The thesis was sponsored, in part, by the NIH Brain Research by Advancing Creative Neurotechnologies (BRAIN) program, which seeks to revolutionize brain knowledge under stable and disease-related conditions.

The thesis was conducted by Lin Tian Lab Researchers, Ph.D., Principal Investigator at the University of California Davis School of Medicine. Present techniques can only track significant differences in serotonin signaling. In this analysis, the researchers turned the nutrient-grabbing bacterial protein Venus flytrap into a highly sensitive sensor that is fluorescently illuminated as it captures serotonin. Previously, scientists at the Loren L. Looger Center, Ph.D., Howard Hughes Medical Institute Janelia Research Campus, Ashburn, Virginia, used conventional genetic engineering methods to transform bacterial protein into a neurotransmitter acetylcholine sensor.

Researchers also explained how sophisticated genetic engineering approaches have been used to turn bacterial proteins into a modern research instrument that can help control serotonin delivery with greater fidelity than current methods. Preclinical studies, mainly in mice, have demonstrated that the sensor can track small, real-time shifts in brain serotonin levels during sleep, anxiety, and social experiences, as well as assess the efficacy of novel psychoactive drugs.

The protein, called OpuBC, usually snags the nutrient choline, which is similar in form to acetylcholine. For this research, the Tian lab collaborated with Dr. Looger’s team and the Viviana Gradinaru lab, Ph.D., Caltech, Pasadena, California, to prove that they wanted the aid of artificial intelligence to fully reinvent OpuBC as a serotonin catcher.

Researchers used deep learning algorithms to help the robot ‘think’ of 250,000 new designs. The scientists decided on one after three rounds of research. Initial tests indicated that the new sensor accurately measured serotonin at various levels in the brain while causing little to no response to other neurotransmitters or related medications.

Experiments in mouse brain slices have shown that the sensor reacts to serotonin signals transmitted by neurons at synaptic contact points. Meanwhile, cell studies in Petri dishes indicated that the sensor could efficiently track changes in these signals triggered by drugs, including cocaine, MDMA (also known as ecstasy), and some widely used antidepressants.

Finally, studies with mice have shown that the sensor may enable scientists to research serotonin neurotransmission in more realistic conditions. For example, the researchers observed a predicted spike in serotonin levels when the mice woke up and fell when the mice fell asleep. They also saw a larger decline as the mice finally reached the deeper resting state of R.E.M.

Orthodox techniques for monitoring serotonin may have skipped these shifts. In comparison, scientists have seen serotonin levels increase differently in two distinct brain anxiety circuits when mice have been warned of a foot shock by a ringing bell. In one circuit – the medial prefrontal cortex – the bell caused a sudden and strong spike in serotonin levels, whilst in the other – the basolateral amygdala – the transmitter increased to significantly lower levels.

In the spirit of the BRAIN project, the researchers are preparing to make the sensor freely accessible to other scientists. They hope it will help researchers develop a greater understanding of the vital position serotonin plays in our everyday lives and in certain psychological disorders.

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