We use our jaws for a variety of purposes, including speaking, singing, coughing, laughing, screaming, yawning, and chewing. Each movement requires complex coordination of muscles, whose activity is managed by neurons in the brain.
But as Rockefeller University researchers explain in a new paper recently published in the journal Nature, the neural circuitry behind the most important jaw movements for survival, and therefore for eating, is surprisingly simple. It turns out. Kristin Kosse and other scientists at the Institute for Molecular Genetics, directed by Jeffrey M. Friedman, have identified three neuronal circuits that link hunger-sensing hormones to jaw movements during mastication. The mediator between these two is a cluster of neurons in a specific area of the hypothalamus that has long been known to cause obesity when damaged.
Surprisingly, inhibiting these so-called BDNF neurons not only causes animals to ingest more food, but also causes the jaws to perform masticatory movements even in the absence of food or other sensory inputs indicating when it’s time to eat. You will be able to: Stimulating them reduces food intake and stops chewing, effectively suppressing hunger.
The simple structure of this circuit suggests that the urge to eat may be more like a reflex than previously thought, providing new clues about how the initiation of feeding is controlled. may be provided.
“It’s surprising that these neurons are so important for motor control,” says Christine Cosse, lead author of the study and a research associate in the lab. “We didn’t expect that restricting physical jaw movement would act as a kind of appetite suppressant.”
Is it more than emotion?
The urge to eat is caused by a variety of factors, not just hunger. We also eat for pleasure, community, ritual, and custom. And smell, taste, and emotions can also influence whether you eat. In humans, eating is also regulated by a conscious desire to consume more or less. The causes of obesity are similarly complex, the result of a dynamic interplay of diet, environment, and genes. For example, mutations in some genes, such as the hunger-suppressing hormones leptin and brain-derived neurotrophic factor (BDNF), cause severe overeating, altered metabolism, and extreme obesity, and both factors usually suppress appetite. It suggests that.
When Friedman’s team began this study, they sought to pinpoint the location of the BDNF neurons that inhibit overeating. BDNF neurons are also a key regulator of neuron development, differentiation, and survival, and their ubiquity in the brain has eluded scientists for years.
The study focused on the ventromedial hypothalamus (VMH), a deep brain region associated with glucose regulation and appetite. It is well established that damage to the VMH, similar to mutated BDNF protein, can lead to overeating and ultimately obesity in animals and humans. Perhaps VMH played a regulatory role in feeding behavior.
By documenting the effects of BDNF on eating behavior, they hoped to discover the neural circuitry that underpins the process of converting sensory signals into jaw movements. They then discovered that when animals became obese, BDNF neurons were activated in the VMH, but not elsewhere. This suggests that BDNF neurons are activated when weight increases to suppress food intake. Therefore, if these neurons are missing or if there is a mutation in BDNF, the animal becomes obese.
chew food without eating
In a series of experiments, the researchers used optogenetics to express or inhibit BDNF neurons in the ventromedial hypothalamus of mice. When the neurons were activated, the mice stopped eating altogether, even when they knew they were hungry. Silencing the rats had the opposite effect: They started eating and kept eating and eating, eating nearly 1200% more food than normal in a short period of time.
When we saw these results, we initially thought that perhaps BDNF neurons encode valence. We wondered if modulating these neurons would cause the mice to experience the negative emotion of hunger, or the positive emotion of eating delicious food. ”
Christin Kosse, first author
However, subsequent experiments disproved that idea. Activating BDNF neurons suppresses food intake, whether the mice are fed standard chow or the mouse equivalent of chocolate mousse cake, which is rich in fat and sugar. The researchers found that
And because hunger isn’t the only motivator for eating, they fed highly palatable food to mice that were already well-fed, as anyone who can’t eat dessert can attest. The animals continued eating until the researchers suppressed the BDNF neurons, at which point they quickly stopped eating.
“This was a perplexing finding at first. Previous research has shown that this ‘hedonic’ urge to eat for pleasure is associated with eating to suppress the negative emotions and negative valence associated with hunger. “It was suggested that this was something completely different from the hunger drive,” Kosse said. “We demonstrated that activating BDNF neurons can suppress both drives.”
Equally impressive, inhibiting BDNF led the mice to use their jaws to chew on any nearby object, even when food was unavailable. This urge to bite and chew was so strong that the mouse chewed on everything around it: the metal spout of a water dispenser, blocks of wood, and even the wires that monitor neural activity. Ta.
circuit
But how does this motor-controlled switch connect to our body’s desires and desire for food?
By mapping the inputs and outputs of BDNF neurons, the researchers found that BDNF neurons are the linchpin of a three-part neural circuit that links the hormonal signals that regulate appetite with the movement required to consume it. I discovered that.
At one end of the circuit are special neurons in the arcuate nucleus (Arc) region of the hypothalamus that receive hunger signals such as the hormone leptin, which is produced by fat cells. (High levels of leptin mean the energy tank is full; low levels of leptin indicate it’s time to eat. Animals without leptin become obese.) Arc neurons It projects to the ventromedial hypothalamus, where signals are received by BDNF. The neurons project directly to a brainstem center called Me5, which controls the movement of the jaw muscles.
“Other studies have shown that when you kill Me5 neurons during mouse development, the mice become unable to chew solid food and starve,” Kosse says. “So it makes sense that if you manipulate the BDNF neurons that project there, you’ll see jaw movement.”
This also explains why damage to the VMH causes obesity, Friedman says. “The evidence presented in our paper shows that the obesity associated with these lesions is the result of the loss of these BDNF neurons, and this finding connects known obesity-causing mutations to a relatively consistent circuit. ”.
This finding suggests something deeper about the relationship between sensation and behavior, he added. “The architecture of the feed circuit is not that different from the architecture of the reflector circuit,” Friedman says. “This is surprising because eating is a complex behavior, and many factors influence whether you will initiate the behavior, none of which guarantee it. Reflexes, on the other hand, are simple: a defined stimulus and an unchanging response.In a sense, this paper shows that the line between action and reflex is perhaps more blurred than we think. We hypothesize that neurons in this circuit are targets for other neurons in the brain that transmit other signals that regulate appetite.”
This hypothesis is consistent with the work of neurophysiologist Charles Sherrington in the early 20th century. He pointed out that coughing is regulated by typical reflexes, but can also be regulated by conscious factors, such as the desire to suppress coughing in a crowded theater.
Dr. Kosse said, “Because feeding is so essential for basic survival, this circuit that regulates food intake may be ancient. Perhaps this arises as the brain evolves. , it may have been the substrate for increasingly complex processing.”
To that end, the researchers say that in the future, jaw motor control may become a useful model for understanding other behaviors, including compulsive and stress-related oral behaviors such as pencil gnawing. The idea is to investigate an area of the brainstem known as Me5. erasers and hair.
“By examining these premotor neurons in Me5, we may be able to understand whether there are other centers that project to this region and influence other innate behaviors, as BDNF neurons do with eating.” ” she says. “Are there neurons that are activated by stress and other neurons that project to them as well?”
sauce:
Reference magazines:
Kosse, C. and others. (2024). Subcortical trophic circuits linking interoceptive tubercles to jaw movements. Nature. doi.org/10.1038/s41586-024-08098-1.
