Scientists Inject Ferrets' Brains With Rabies to Study … Vision?
When ferrets get a rabies shot in a neurobiology lab, they don't get infected with the virus—or even inoculated against it. They get a brain hack that might just explain how your brain handles vision, and maybe even your other senses, too.
In a lab at Dartmouth, scientists are experimenting with targeted injections of a modified rabies virus into the brains of ferrets—essentially allowing them to control how the animal responds to simple visual patterns. The goal is to understand the brain's enormously complex visual processing system. But really? Rabies? Ferrets? Are these guys just screwing around?
Lots of visual research depends on lab mice—the most popular of model organisms in biology. But Dartmouth neuroscientist and lead author Farran Briggs wanted to study an animal that uses its vision the same way humans do, in an evolutionary sense: to prey on tasty snacks. Mice aren’t predators, and their vision falls solidly in the ‘legally blind’ range. So these vision researchers turned to the notoriously vicious ferret and its front-facing eyes. They're color blind, but at the neural level, ferrets’ visual systems have “remarkable similarities to a primate, and a human,” says Briggs. (Ferrets also help avoid the ethical issues of experimenting on primates.)
The classic approach to understanding visual circuits would be to find a way to switch off part of the system, and see what changes. That’s one reason why mouse models are great: Scientists have figured out how to breed mice with light-sensitive instructions inserted next to specific genes—a relatively new field called optogenetics—so that neurons with that specific gene will turn on when exposed to light. Biologists don't have the same systems for genetic control in ferrets, though, so Briggs and her team figured out a different way to engineer light-controlled brain bits.
In this case, they used rabies—not so much a a virulent pathogen here as an on-off switch for neurons. When an animal gets rabies, the virus sneaks into nerve cells thanks to special protein coating that acts like a secret, neuronal password, and Briggs and her team capitalized on that entry system. With help from the Salk Institute scientists who invented this technique, they plunked a light-sensitivity gene into the rabies virus and stripped off its coat-protein genes. Then they covered their modified virus in just enough protein to enter one cell, and injected it into the part of the ferret’s brain they were interested in. “Once those viruses get into those neurons, they’re stuck,” says Briggs. The virus makes the neurons light-sensitive, but otherwise keeps to itself.
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Specifically, Briggs and her team wanted to look at the place in the brain where the cortex whispers to another brain region called the thalamus. One of the first steps of visual processing is a feedback loop between these two regions, which starts when light bounces into your eye. Your retina signals the thalamus, which calls out to the cortex, which in turn sends a message to the thalamus via long, neuronal tendrils. “For decades, basically, we haven't really had a great handle on the role of these kind of projections,” says Ben Scholl, a researcher at the Max Planck Florida Institute for Neuroscience.
Once those projections were inoculated with rabies, Briggs and Co. could switch them on by flashing a blue LED. Tracking the cortex and thalamus' activity with electrodes, they showed anesthetized ferrets statistically controlled TV noise and watched how visual processing changed. They saw that cortex feedback made the thalamus respond more quickly and precisely than when those feedback neurons were disengaged.
Briggs had expected an amplification in the signal, but instead saw a change in the speed and quality of signaling. And although this is just one circuit in the pathway of processing sensory information, it’s possible that interactions like this one might point to design rules that apply to other feedback loops, as well, says Scholl.
So, no, these guys aren't just messing around. Understanding the way the brain works is so complicated that researchers have had to come up with complicated, highly specialized methods like these to isolate pieces of the puzzle. Maybe one day, armed with more rules for these types of circuits, researchers will be able to nail down an idea of how your brain lets some information fade, while other signals get cranked to 11. Until then, you can expect lots more weird neuroscience dispatches.
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