If the idea of driving down a winding road makes you feel queasy, spare a thought for the mice employed in a new study, which sought to pinpoint the brain cells responsible for motion sickness.
Unsuspecting mice were plopped in a plastic tube, strapped onto a rotating spinner, and sent for a ride, so researchers could pinpoint which neurons lit up after this nausea-inducing merry-go-round.
The animals' body temperature dropped, and they shunned food and cowered in their cages – all clear signs that they were experiencing something akin to the motion sickness humans do. Cold sweats, anyone?
Based on past research, neuroscientist Pablo Machuca-Márqueza, of the Autonomous University of Barcelona, and colleagues figured they'd start looking at cells in the vestibular nuclei, a bundle of nerve fibers in the brainstem that relay signals from the ear to the brain.
Sensors in our middle ear, as well as our limbs and eyes, feed information to our brains to orientate us as we move. It's thought that a sensory mismatch causes motion sickness: our eyes and inner ear are telling our brain that we're moving when we're not.
Several parts of the brain process sensory inputs from the ear, eyes, and limbs, but little is known about which neurons actually cue motion sickness. Pinpointing them could be a step toward developing more effective medications for motion sickness, with fewer side effects.
To figure out which cells fired in response to motion sickness, Machuca-Márqueza and colleagues inhibited different subsets of neurons within the vestibular nuclei and then strapped the mice back on the spinner to see if those changes alleviated motion sickness.
Round and round the mice spun. Inactivating a group of vestibular neurons that express a protein called VGLUT2 prevented the animals' spin-induced motion sickness.
Switching on those same neurons triggered motion sickness-like behaviors in mice without spinning. Talk about sensory mismatch; that would be a real trip.
Of those VGLUT2-expressing neurons, cells sprouting a receptor called CCK-A were responsible for most motion sickness behaviors in the experiments, the researchers found.
They also mapped the circuitry of these neurons, finding dense projections of CCK-A neurons plugged into the brain's parabrachial nuclei, an area known to regulate appetite suppression, body temperature, and lethargy.
Stimulating these projections brought on some, but not all, signs of motion sickness in the mice. The animals' body temperature fell and they avoided sugary foods, but they still ate and moved normally. So other connections stemming from vestibular nuclei likely induce those bodily responses to motion sickness.
When the researchers blocked the CCK-A receptor with a drug compound before sending mice for a spin, half the number of brain cells in the parabrachial nuclei were active and it alleviated some motion sickness behaviors.
Most anti-motion sickness medications work similarly, to reduce activity in the brain's balance system or limit signals being sent between the brain and gut, to help stop nausea and vomiting.
But these medications are blunt at best. They block chemical messengers that act throughout the body, cause drowsiness, and only tend to work if taken before motion sickness sets in; after that, they are rarely effective.
If the pathways uncovered in this mouse study work the same way in humans, then researchers might have a new, clearer target for quashing movement-induced ills, much to our relief.
The study has been published in PNAS.