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MIT researchers have devised a way to look deeper into the brain than ever before. Calcium is an essential signaling molecule for most cells. It plays an even bigger role in neurons.
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Scientists have long been able to image calcium in brain waves to develop a picture of how they communicate with each other. However, current technology only allows for image penetration of a few millimeters.
MRI helps to get a deeper image
The MIT research team have developed a method based on magnetic resonance imaging (MRI) and provides a much deeper view.
“This paper describes the first MRI-based detection of intracellular calcium signaling, which is directly analogous to powerful optical approaches used widely in neuroscience but now enables such measurements to be performed in vivo in deep tissue,” says Alan Jasanoff, an MIT professor of biological engineering, brain and cognitive sciences, and nuclear science and engineering, and an associate member of MIT McGovern Institute for Brain Research.
While at rest, brain neurons have very low levels of calcium. But when the neurons fire an electrical impulse, calcium floods the neuron.
New method penetrates further
Scientists have used this phenomenon to get an insight into how the brain works by labeling calcium with fluorescent molecules. This is done in brain cells in a lab dish or in the brains of living animals.
However, this kind of microscopy imaging can only penetrate a few tenths of a millimeter into the tissue, which limits the study to just the surface of the brain.
“There are amazing things being done with these tools, but we wanted something that would allow ourselves and others to look deeper at cellular-level signaling,” Jasanoff says.
To achieve their dream, the researchers began looking at the MRI. MRI works by detecting magnetic interactions between an injected contrast agent and water molecules inside cells. It’s a common tool for non-invasive imaging in various parts of the body.
While other research had been done on MRI-base calcium sensors, however, they had been impeded by the lack of development of a contrast agent that can get inside brain cells. Jasanoff team created a contrast agent that used building blocks that can pass through the cell membrane.
Successful testing on rats
The agent contains manganese bound to a compound that can penetrate cell membranes. It also contains a calcium-binding arm called a chelator. Once the agent is inside the cell, if calcium levels are low, the chelator binds weakly to the manganese atom, protecting the metal from MRI detection.
When the cell is flooded with calcium the chelator binds to the calcium and releases the manganese, the contrast agent then appears brighter in the MRI image.
“When neurons, or other brain cells called glia, become stimulated, they often experience more than tenfold increases in calcium concentration. Our sensor can detect those changes,” Jasanoff says.
To test their agent, the researchers injected it into the brains of rats in a deep area of the brain known as the striatum. The striatum is the part of the brain involved in planning movement and learning new behaviors.
Potassium ions were then used to stimulate electrical activity in the neurons of the striatum, and the researcher was able to measure the calcium response in those cells.
The research will continue to be developed and may bring about the chance to precisely understand the timing of neuron activity deep in the brain.
“This could be useful for figuring out how different structures in the brain work together to process stimuli or coordinate behavior,” Jasanoff says. The research appears in Feb. 22 issue of Nature Communications.