Cell interpretation! Scientists have developed new tools to observe and control nerve activity in the brain!

December 21, 2020 // -- In a recent study published in the international journal Cell entitled "A Molecular Calcium Integrator Reveals a Striatal Cell Type Driving Aversion Aversion", scientists from Stanford University and other institutions have developed a new molecular probe, or A tool called "Flicker and Calcium-Regulated Expression; Rapid Light and Calcium Regulatory Expression Technology, or FLiCRE" that can be used to perform a variety of research tasks within any cell, including marking, recording, and controlling cell function, can help reveal the molecular mechanisms of brain thinking and memory.
researcher Alice Ting says the work involves a central goal of neuroscience: how to find the neuron system behind the body's brain's thoughts or cognitive processes. Neuroscientistes have long wanted to find such research tools.
in a proof-of-concept experiment, the researchers used the FLiCRE tool to take snapshots of neuroactive activity associated with avoidance behavior in mice.
by combining FLiCRE snapshots with RNA sequencing techniques, the researchers found that the activated neurons belonged primarily to a single cell type that was not available using genetic tools alone.
Then the researchers combined the FLiCRE tool with the visual protein opsin, a special protein that uses light to control nerve activity, to reactivate the same neurons a day later, which may have caused the mice to avoid entering a room, and the brain region studied by the researchers, known as the nucleus accumbens, is thought to play a key role in the development of a variety of human mental illnesses, including depression.
image source: CC0 Public DomainFLiCRE consists of two main molecular components that react to blue light and calcium.
This light sensitivity allows researchers to precisely control the timing of experiments, and calcium is almost a universal indicator of cellular activity; in order for FLiCRE to enter the cell, the researchers package two parts of it in harmless viruses, a portion of FLiCRE adheres to the cell membrane, and the protein it contains enters the nucleus and drives the gene of the researchers' choice to express it;
Current labeling techniques take several hours to activate, while FLiCRE's marking process takes only a few minutes, so researchers designed FLiCRE to be able to use standard gene sequencing techniques to find cells that can be activated by FLiCRE, which can help them study tens of thousands of cells at once, while other techniques often require analyzing multiple microscopic images, each containing hundreds of cells.
In a series of experiments, the researchers injected FLiCRE into cells in mice's volt-kernels and used opsin proteins to activate neural circuits associated with mouse avoidance behavior; If the mice were avoiding the cellular indicators of something, the cells would glow permanently red and could be observed through a microscope, and the researchers sequenced the cell's RNA to see which cells contained fluorescent proteins and could produce cell-by-cell records of nerve activity.
researcher Christiana Kim points out that our goal is to map the connections between brain regions in living animals, but this is a very difficult problem, and the benefit of the FLiCRE tool is that it helps us pulse and activate neurons in one region and then record all connected downstream neurons, which may be an effective way to help observe long-distance brain activity connections.
In a follow-up experiment, the researchers used cell activity maps obtained from the first experiment, and they adjusted FLiCRE so that proteins can express the opsin protein, which is also controlled by orange light to alter the activity of neurons; After LiCRE, the researchers used fiber-optic implants to emit orange light each time the mice entered a particular room, and in response, the mice avoided the room, suggesting that FLiCRE did identify the specific cells in the brain that drive the body's avoidance behavior.
The development and testing of FLiCRE combines chemistry, genetics, biology, and neuroscience with many other disciplines within these disciplines, so researchers believe that FLiCRE tools have a wide range of applications, including research on cells other than the brain.
researchers are currently working on other versions of FLiCRE to streamline the process; researchers hope to simplify its structure so that it can work with other bio-chemical events, such as protein interactions or neurotransmitter release.
() References: (1) Christina K. Kim, Mateo I. Sanchez, Paul Hoerbelt, et al. A Molecular Calcium Integrator Reveals a Striatal Cell Type Driving Aversion, Cell (2020). DOI: 10.1016/j.cell.2020.11.015【2】New tool for watching and controlling neural activityby Stanford University。