- Neuroscientists have developed a technique to map neural activity pattern with resolution and specificity that conventional MRI cannot achieve.
- The new probe, made of magnetic calcium-responsive nanoparticles using synaptotagmin proteins, enables larger volumes of brain-tissues to be measured.
Functional Magnetic Resonance Imaging (fMRI) is a well-known method that uses powerful radio waves, magnets and a computer to make detailed images of your body parts. It usually detects neurophysiology indirectly through blood-flow changes.
So far, scientists have made MRI-detectable calcium-responsive nanoparticle sensors for non-invasive applications. However, none of them has been able to show calcium dynamics in living organisms.
One of the major obstacles in developing a calcium sensor is the requirement of a sensor technique that transduces modest analyte fluctuations into detectable alterations in the image signal. It’s very difficult to reach such sensitivity level using sensors made of small molecules.
Now MIT neuroscientists have found a way to improve on previous techniques by utilizing the highly cooperative sensing approach through reversible magnetic nanoparticle clustering. In simple language, they have built a new MRI sensor for monitoring neural activity in the brain by tracing calcium ions.
How Calcium Ions Helps In Monitoring Neural Activity?
Scientists have devised a method to map neural activity patterns with resolution and specificity that fMRI cannot achieve. They used calcium ions directly connected to neuronal firing — a new kind of sensing technique — to link particular functions of the brain to their neuron activity patterns, and to show how different parts of the brain communicate with each other while performing specific tasks.
Signaling event in the nervous system highly depends on the concentration of calcium ions. A new probe with molecular architecture built by neuroscientists is capable of sensing subtle alterations in extracellular calcium.
Sensors prepared by mixing fused C2 domains of synaptotagmin 1 (C2AB) with lipid-coated iron oxide nanoparticles
How It Works?
Calcium ions usually rush into a cell when neurons fire electrical impulses. For almost 10 years, fluorescent molecules have been used to label calcium within the brain and map it with conventional microscopy. Although the approach enables precise tracking of neuron activity, it’s limited to small regions of the brain.
The new probe, made of magnetic calcium-responsive nanoparticles (MaCaReNa) using synaptotagmin proteins, enables larger volumes of tissues to be measured. It can identify subtle alterations in concentrations of calcium outside of cells, and acknowledge in a manner that can be observed with MRI.
This calcium-responsive sensor contains 2 types of clustered-particle:
- Synaptotagmin – a calcium-sticking protein that occurs naturally.
- A nanoparticle of magnetic iron oxide coated in a lipid, which can also be bound to synaptotagmin in the presence of calcium.
These particles assemble together due to calcium binding, thus leaving darker spots in MRI. High neuron activity shows low level of calcium outside the neurons – when neurons fire electrical impulses, the concentrations of calcium decrease in that particular region.
In a series of tests [performed on rats], they demonstrated that this newly developed calcium sensor can precisely identify changes in neural activity caused by electrical or chemical stimulation.
Dynamic calcium ion fluctuations in living rat brains
More specifically, they injected these sensors into rats’ striatum — a part of the brain responsible for learning new behaviors and planning movements — and provided them a chemical stimulus for inducing small spell of neural activity. They found that the calcium sensor picked up activities caused by electrical stimulation.
These calcium-responsive sensors take a few seconds to respond after the initial brain stimulation. However, scientists are trying to speed up the process and enhance the sensor so that it could work for a wider area of the brain. Moreover, if they could make the sensor pass through blood-brain barrier, they would be able to send the particles without having to directly inject them to the test site.
Future applications of calcium-dependent sensor include characterizing extracellular calcium signaling in animal models, techniques that govern calcium ion fluctuations and relationships of extracellular calcium to diverse biological phenomena in the brain and other parts of the body.