U.S. government scientists have developed a miniature, wearable brain scanner for rats—dubbed “RatCAP”—that allows accurate brain imaging to be done while animals are awake and moving. They expect the device will greatly expand the use of brain imaging to study behavior.
“The behavioral neuroscientists that we talk to are very excited about the possibility that, now, they can see what’s going on in the brain while they’re doing their behavioral measurements,” says Paul Vaska, a physicist at Brookhaven National Laboratory who led the team of scientists and engineers that developed RatCAP. The team described the device in the April issue of Nature Methods.
“It opens a whole new approach to studying behavior in animals that we didn’t really have before,” says William Jagust, a brain-imaging researcher at the University of California - Berkeley and Lawrence Berkeley National Laboratory who wasn’t involved in the Brookhaven research. “We now might be able to see, for example, differences in neurotransmitter systems in animals’ brains when they’re being trained to do certain kinds of tasks, or receiving certain kinds of rewards.”
Small positron-emission tomography (PET) scanners for lab mice and rats have been available for years, but they have had two major limitations. First, they are too bulky to be wearable; and second, to get clear images they require that the animal be immobilized, which means that the animal must also be anesthetized to reduce its stress. Both immobilization and anesthesia tend to alter brain activity in ways that defeat the purpose of behavioral experiments.
“Our approach was to miniaturize the scanner so that it could be attached to the animal’s head, allowing it to move around,” says Vaska.
The RatCAP (“conscious animal PET”) device is a miniature version of a PET scanner shaped like a metal collar to fit around a rat’s head. The scanner can be worn by rats within their usual lab cages. PET scanners can follow radioactive particles introduced into the brain to trace its activity. To prevent blurring of images, the device is fixed—relatively painlessly, it appears—to a rat’s skull. At a half-pound in weight, it is still too heavy for a rat to carry around without assistance; but the researchers made it feel nearly weightless by suspending it from a springy, pendulum-like apparatus above each rat’s cage.
Vaska and colleagues showed that they could scan awake rats with the device and get sharp images of target brain regions, using a standard PET tracer, raclopride, that binds to dopamine D2 receptors on brain cells without activating them. (More raclopride binding, for example, implies more D2 receptor availability and thus less innate dopamine-D2 signaling.) Their image data from the striatum, a motion-related brain region, correlated well with the rats’ spontaneous behavior, even when averaged over an hour-long scanning period—as is typical for PET scans.
A wearable PET scanner would be even more useful if it could register brain data over much shorter spans of time. Vaska and his team tried to do this by keeping a test rat’s brain levels of the tracer fairly constant with an infusion device, and then measuring changes from this equilibrium level. “It actually worked,” says Vaska. “We saw a correlation between the PET data and the rat’s behavior, essentially on a minute-by-minute basis, which is pretty surprising—people haven’t used PET for that before.”
These novel experiments also hinted at a new finding concerning raclopride’s interaction with the dopamine system. The tracer is typically used in addiction experiments, when drugs such as cocaine cause a flood of dopamine in the brain. In such high-dopamine situations, raclopride-PET seems principally to measure activity at one class of D2 receptors—whereas in this case, involving much more subtle interventions and dopamine responses, raclopride-PET appeared mainly to mark the activity of a different and perhaps more sensitive class of D2 receptors—feedback “autoreceptors” that are involved in dialing down excessive dopamine secretion. “That’s our hypothesis, anyway, though it’s impossible to prove with the data we have so far,” says Vaska.
Having shown that the RatCAP device can work, Vaska and his group now plan to refine it and apply it to certain basic rat behaviors. “I think the next study will be on sexual behavior, because that’s a pretty clear behavior, and it also should have a strong effect on dopamine levels,” says Vaska.
The device isn’t limited to use with raclopride; in principle, it could be used with a variety of PET tracers to probe a range of receptors and other molecular targets in the brain. Vaska says he also has thought about developing a wearable PET device for human subjects, which would enable near-real-time brain imaging to be taken during otherwise uncontrollable brain events, such as epileptic seizures or schizophrenic hallucinations: “It would definitely take a lot of work—not just building the scanner, but also developing the methods to analyze the data—but it’s definitely something to consider.”