MIT neuroscientists have developed a new magnetic resonance imaging (MRI) sensor that can monitor calcium activity in the deep brain. This sensor experiment will provide scientists with more powerful means of observing the brain and will promote the in-depth development of neuroscience and computer science.
Other types of MRI obtain information on neuronal activity by detecting changes in blood flow, whereas changes in blood flow merely provide indirect signals of neural activity. While calcium ions are directly involved in neuronal activity, this new type of sensor allows researchers to relate specific brain functions to their neuronal activity patterns and to determine the communication distance between different brain regions during a specific task.
"The concentration of calcium ions is closely related to the signal events in the nervous system," said Alan Jasanoff, professor of MIT's Department of Bioengineering, Brain and Cognitive Science, and Nuclear Science and Engineering. He is also a member of the McGovern Institute for Brain Research at the Massachusetts Institute of Technology. The associate member is also a senior researcher in the study. "We designed a probe with a molecular structure that can detect relatively subtle changes in extracellular calcium ions associated with neural activity."
In rat experiments, the researchers said that their calcium sensors can accurately detect changes in nerve activity caused by chemical or electrical stimuli, which are located deep in the brain's site called the striatum.
MIT researcher Satoshi Okada and Benjamin Bartelle are the lead authors of the study, published in the April 30th issue of Nature Nanotechnology. Other authors include members of the Picower Institute of Learning and Memory, Professor of Brain and Cognitive Science, Mr. Lignan, research assistant Li Nan, postdoctoral fellow Vincent Breton-Provencher, former postdoctoral Elisenda Rodriguez, Wellesley College undergraduate Li Jiying, and high school student James Melican.
Trace calcium ions
MRI is a pillar tool in neuroscience research that allows scientists to identify the active parts of the brain in specific tasks. The most commonly used type of MRI, called functional MRI, measures neural activity by measuring cerebral blood flow, an indirect marker of neural activity. Jasanoff and his colleagues wanted to design a method that could map neural activity more specifically and with high resolution that could not be achieved with MRI technology that recognizes changes in blood flow.
"The ability to map brain activity in deep tissue depends on changes in blood flow, and blood flow interacts with nerve activity in many different physiological pathways," Jasanoff said. "So, the signals you end up seeing are often very Hard to attribute to a specific factor. "
The flow of calcium can be directly linked to neuronal activity. When the neuron emits an electrical pulse, calcium ions will pour into the cell. For about a decade, neuroscientists have been labeling calcium in the brain with fluorescent molecules and imaging them with a traditional microscope. This technique can accurately track neuronal activity, but its use is limited to a very small part of the brain.
MIT's research team began looking for a method of magnetic resonance imaging of calcium ions, which can analyze larger tissue volumes. To do this, they designed a new sensor that responds to subtle changes in extracellular calcium concentration and whose response can be detected by MRI.
This new type of sensor consists of two types of particles that can be clustered together when calcium ions are present. One of these two types of particles is the naturally-occurring calcium-binding protein synaptotagmin, and the other is a magnetic iron oxide nanoparticle encapsulated in fat, which binds to synaptotagmin but only when calcium is present.
The presence of calcium induces the aggregation of these particles, making them appear darker in MRI images. When the activity of neurons is low, the content of extracellular calcium in the neurons is high. When the concentration of calcium is decreased, it means that the neurons in this area must send electrical pulses.
Detect brain activity
To test these sensors, the researchers injected them into the striatum of rats (the striatum is the area where planning movements and learning new behaviors). They then applied to mice a chemical stimulus that induced short-term neural activity. It was observed that the calcium sensor recorded this activity.
They also found that this sensor can capture activity triggered by reward-related electrical stimulation signals in parts of the brain.
"This method provides a new way to study brain function," said Xin Yu, a research team leader at the Max Planck Institute of Biological Cybernetics. He did not participate in the study.
"Although we have accumulated enough intracellular calcium signal knowledge in the past half century, few people have exactly studied the contribution of extracellular calcium dynamic changes to brain function, or how extracellular calcium signals indicate the function of the brain. Xin Yu said, "When we decipher a complex and adaptive system like the brain, every piece of information is very important."
The current sensor responds within seconds of initial brain stimulation, but researchers are thinking to make it more responsive. They are also trying to modify the sensor so that the particles can spread to a wider area of ​​the brain and pass through the blood-brain barrier, which will enable sensor delivery without having to inject them directly into the area to be tested.
With this sensor, Jasanoff hopes to draw a pattern of neural activity more precisely than it does now. He said: "Imagine that you can measure the activity of calcium ions in different parts of the brain and try to determine that different types of sensory stimuli encode differently through the spatial patterns of the neural activities they induce."
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