Controlling the transmission and reception of signals in brain circuits is necessary for neuroscientists to gain a better understanding of the functions of the brain. Communication between neurons and glial cells is mediated by various neurotransmitters released from vesicles by exocytosis. Thus, the regulation of vesicular exocytosis may be a possible strategy to control and understand brain circuits.
However, it has been difficult to freely control brain cell activity in a spatiotemporal fashion using pre-existing techniques. One is an indirect approach of artificially controlling the membrane potential of cells, but it comes with problems of altering the acidity of the surrounding environment or unwanted misfires of neurons. In addition, it is not applicable for use in cells which do not respond to changes in membrane potential, such as glial cells.
To solve this problem, South Korean researchers led by Director C. Justin LEE of the Center for Cognition and Sociality at the Institute for Basic Science (IBS) and Professor HEO Won Do of the Korea Advanced Institute of Science and Technology (KAIST ) have developed Opto-vTrap, an inducible and reversible inhibition system that can temporarily prevent vesicles from being released from brain cells. Opto-vTrap directly targets transmitters containing vesicles and can be used in various types of brain cells, even those that do not respond to changes in membrane potential.
In order to directly control exocytotic vesicles, the research team applied a technology it had previously developed in 2014, called Trap Assembled Light Activated Reversible Inhibition (LARIAT). This platform can inactivate various types of proteins when illuminated under blue light by instantly trapping target proteins, such as a lariat. Opto-vTrap was developed by applying this LARIAT platform to exocytosis of vesicles. When cells or tissues expressing Opto-vTrap are illuminated with blue light, the vesicles form clumps and become trapped in the cells, inhibiting the release of transmitters.
More importantly, the inhibition triggered using this new technique is temporary, which is very important for neuroscience research. Other prior techniques that target vesicle fusion proteins permanently damage them and deactivate the target neuron for up to 24 hours, which is not appropriate for many behavioral experiments with short time constraints. In comparison, vesicles that were inactivated using the Opto-vTrap decluster in about 15 minutes, and neurons return to full function within an hour.
Opto-vTrap directly controls the release of signal transmitters, allowing researchers to freely control brain activity. The research team verified the ease of use of Opto-vTrap in cultured cells and brain tissue slices. Additionally, they tested the technique on live mice, which allowed them to temporarily suppress fear memory in fear-conditioned animals.
In the future, Opto-vTrap will be used to discover complex interactions between several parts of the brain. It will be a very useful tool to study how certain types of brain cells affect brain function under different circumstances.
Professor Heo said, âSince Opto-vTrap can be used in various types of cells, it should be useful in various areas of brain science research,â he explained, âWe plan to to conduct a study to determine spatiotemporal brain functions in different types of brain cells in a specific environment using Opto-vTrap technology. “
âThe usability of Opto-vTrap can extend not only to neuroscience, but also to our lives,â says Director Lee. He added, âOpto-vTrap will not only help elucidate brain circuit mapping, but also epilepsy treatment, muscle spasm treatment and skin tissue expansion technologies. “
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