Neuron Paths

A new scanning technology will allow us to map the growth pathways of neurons as they develop in living brains, a recent study reports.

Mouse brains, having a neuroblast. (Sorry, I had to say it.)

The patented technique is based on fMRI – but instead of tracking patterns of blood flow like an ordinary MRI, it tracks a special protein called ferritin, which is introduced into certain neurons via an engineered virus. As some cells begin to produce more ferritin, they harvest and store more iron, which changes their magnetic fields, making them easier to pick up on fMRI scans. It’s a pretty clever workaround for an age-old problem.

See, the difficulty with studying individual neurons – especially those deep within the brain – is that many deep scanning technologies like fMRI are only precise enough to detect fairly large groups of neurons firing together. So for decades, the only way to examine individual neurons in detail was to take thin slices of the brain and study them beneath a microscope. But because this new technology makes specific neurons light up on an fMRI scan, it represents a major leap forward in targeted brain imaging.

As the journal Nature Medicine reported back in 2005, a team led by Carnegie Mellon’s Eric Ahrens first used ferritin to map full-grown neurons – but in this latest study, the journal NeuroImage reports, Ahrens and his team have placed ferritin in neuroblasts, neural stem cells that may develop into neurons or neuroglia. This allowed them to track the paths of young cells as they migrated into place and developed into their “adult” forms:

Here, we describe an efficient ferritin-based magnetic resonance imaging (MRI) reporter and its use to label mouse subventricular zone progenitors, enabling in vivo visualization of endogenous neuroblast migration toward the olfactory bulb. We quantify the effect of the ferritin transgene expression on cellular iron transport proteins such as transferrin receptor, divalent metal transporter and STEAP reductase.

In short, by triggering neuroblasts to manufacture ferritin, they were able to watch the progress of those cells as they migrated into the olfactory bulb of a rat’s living brain, and continued to grow there.

The way the researchers introduced the ferritin into the neuroblasts is also pretty cool: first they engineered a new form of the protein that was especially easy to detect on an fMRI scan. Then they inserted that protein’s DNA sequence into an adenovirus, and infected neuroblasts with that virus. Thus, the growing cells produced more ferritin on their own, allowing the fMRI scan to detect them in real time as they moved and grew throughout the brain:

This MRI reporter gene platform can facilitate the non-invasive study of native or transplanted stem cell migration and associated neurogenic or therapeutic molecular events in live animals.

The researchers hope this new technology will provide a much more detailed understanding of how newborn neuroblasts shape the growth of the brain – maybe months down the line, or even after the cells have died. Eventually, technologies like this might help doctors redirect neuronal growth to damaged areas of the brain.

And at last, like worried parents, scientists will finally be able to tell exactly where their little neurons are at all times.

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