Gnaw-y by nature: Researchers discover neural circuit that rewards gnawing behavior in rodents

(Press-News.org) Researchers at the University of Michigan have discovered that the constant gnawing of rodents isn't just a reflex or a consequence of a tough diet. It also triggers a release of dopamine in the brain—which acts as a biochemical reward or incentive—through a newly identified neural circuit.

Although the circuit was discovered in mice, it could also be at work in other mammals, the researchers said, adding to a growing body of evidence that there's a deeper connection between our brains and our oral health and habits.

"In the old point of view, everyone sort of believed that gnawing was a very passive behavior driven by mechanical considerations," said Bo Duan, associate professor in the U-M College of Literature, Science, and the Arts Department of Molecular, Cellular and Developmental Biology. Duan led the study with Joshua Emrick, assistant professor at the U-M School of Dentistry.  

"What we're learning is that this is indeed a motivated behavior. There is a defined neural circuit that connects sensory input from the teeth to dopamine neurons in the midbrain," Duan said. "This tells us that even very basic maintenance behaviors are actively reinforced by the brain." 

He added that identifying the circuit provides a concrete biological explanation for why these repetitive behaviors are sustained over time. This connection could help explain why dogs chew bones and why people bite their nails. 

On the human health front, dopamine regulation has also been implicated in oral issues. That includes bruxism, the medical term for involuntarily grinding or clenching your teeth, and malocclusion, which are when a patient's upper and lower teeth are misaligned.

The team's discovery, published in the journal Neuron, could help lead to more effective interventions for such conditions in revealing the connection between sensations in the mouth and dopamine releases in the brain.

"I think the most lasting impact of this is that it helps us understand why animals have repetitive oral behaviors and how that relates to human pathology," said Emrick, a dentist and sensory neuroscientist who works in the Department of Biologic and Materials Sciences and Prosthodontics.

"If you have a malfunction in the system at a higher level, it ultimately can be very destructive for our oral tissues and, honestly, we don't have targeted  treatments for the underlying issue. We need a fundamental understanding of how and where these behaviors are being driven in the brain."

The study was supported by federal funding from several of the National Institutes of Health, including the National Institute of Neurological Disorders and Stroke and the National Institute of Dental and Craniofacial Research.

Always be chomping

For rodents—an order of mammals that includes mice, rats, squirrels, beavers, groundhogs, capybaras—incessant gnawing is a way of life (the word rodent comes from the Latin "rodens," which means "gnawing"). Their incisors grow continuously throughout their lives, so they gnaw to keep their teeth at a healthy length and shape, which in turn maintains their jaw alignment. Without that alignment, eating becomes difficult, if not impossible.

The prevailing understanding had been that this behavior was driven by reflex for mechanical maintenance in a rodent's mouth and their choice of hard substrates. But Duan's team, which uses mouse models to study neural circuits underlying touch and somatosensation, began to notice that some of their experimental animals were becoming long in the tooth. 

"That observation suggested to us that something beyond a simple reflex might be involved," Duan said.

Recognizing that abnormal tooth overgrowth might reveal something more than a simple reflex, Duan partnered with Emrick who studies oral and craniofacial sensation to investigate the phenomenon more deeply and explore its broader oral health implications.

Their collaboration revealed that touch-sensitive neurons in the tissue around teeth send signals to a junction that connects to two distinct paths. One is to motor neurons that help move the jaw and position its incisors—that's the sort of mechanical component. The other extends into the midbrain where it activates a dopamine center, giving rise to the motivational component of the behavior.

"If you block the motivation pathway, the sensory-motor pathway is still intact and that does help maintain teeth," Duan said. "But, without the motivation, it's just not very efficient. So the motivation part is very important."

In the case of rodents, that motivation is key to keeping their teeth in check and their jaws aligned, ensuring they'll be able to eat normally to survive. 

"Even though human teeth stop growing, the brain mechanisms that drive repetitive oral behaviors may still be operating," Duan said. "Understanding this circuit helps us see how sensory signals from the mouth influence motivation and, potentially, oral health." 

Previous studies have shown that people with conditions that affect their motivation and behavior, including autism and depression, experience higher than average instances of malocclusion. Furthermore, Emrick said, Parkinson's disease and its treatments affect the brain's dopamine levels and when patients are given continued dopamine precursors as part of their treatment, they can develop bruxism in the long-term.

"Now we have the evidence for a biological circuitry link that may be contributing," Emrick said. 

The new circuit provides a concrete example of a possible answer, which could potentially create new pathways to treating these issues. The team is also interested in if the circuit could explain gnawing habits in other animals.

"If you look across mammals, there's something about oral tone that needs to be maintained—even if you're an animal without ever-growing incisors. Keeping your musculature in shape is incredibly important because you need to acquire and consume foods," Emrick said. "We came in with a curiosity to understand this peculiar feature of rodents—gnawing—and this led us to a new understanding of neural processes that affect human health. Part of our motivation is to make fundamental discoveries and direct those toward human health."

Duan said the team is now exploring whether similar sensory-reward pathways regulate other behaviors beyond gnawing. 

"We think this may represent a more general principle," he said. "Understanding how these circuits are organized could eventually help us target them when the behavior becomes maladaptive."

Researchers from the U-M Life Sciences Institute, Department of Mechanical Engineering, Department of Cell and Developmental Biology, and Department of Molecular and Integrative Physiology also contributed to the study.

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