American researchers have discovered a surprisingly simple brain circuit made up of just three types of neurons controlling chewing movements in mice and also having a surprising impact on their appetite.

“It is surprising that these neurons are so linked to motor control,” said Christin Kosse, neuroscientist at Rockefeller University.

“We didn’t expect that limiting physical jaw movements could act as a sort of appetite suppressant.”

Damage to ventromedial hypothalamus the brain region was already known to cause obesity in humansKosse and his colleagues therefore took a closer look at the neurons in this part of the brain in mice. Previous studies had shown disruptions in their expression of a protein called brain-derived neurotrophic factor (BDNF) was linked to metabolism, overeating and obesity.

The researchers used a process called optogenetics to activate BDNF neurons in some mice, causing the rodents to lose virtually all interest in food. Their disinterest persisted whether they were full or hungry. They even ignored the temptation of a fatty and sugary treat, equivalent to a delicious chocolate cake.

“This was initially a puzzling finding, because previous studies suggested that this ‘hedonic’ drive to eat for pleasure was very different from the hunger drive, which is an attempt to suppress negative feeling, or negative valence, associated with hunger while eating. explain Kosse. “We demonstrated that activation of BDNF neurons can suppress both drives.”

This suggests that BDNF neurons occupy a place further along the decision-making pathway, between chewing and not chewing.

In contrast, inhibiting the BDNF neural circuit in mice significantly increased their compulsion to move their jaws and gnaw everything, including indigestible things like their water bottle and monitoring equipment. Additionally, when food was available, they consumed 1,200 percent more than normal in a given time frame.

Consistent with previous findings on the potential role of BDNF in eating, the results suggest that these neurons and the chemicals they produce generally suppress appetite unless other bodily signals, like our hunger, tell them not to do it.

Kosse and his team discovered that BDNF neurons receive information about the state of our interior from sensory neurons, including a variety known to create the feeling of hunger. Leptin is one of the key signaling molecules used here, which is also known for its involvement in hunger and obesity.

BDNF neurons then regulate the pMe5 motor neurons that make our jaws chew, based on this sensory information.

“Other studies have shown that when Me5 neurons are killed in mice during development, the animals will starve because they are unable to chew solid foods,” said Kosse. “So it makes sense that when we manipulate the BDNF neurons that project to it, we would observe jaw movements.”

Isolating BDNF neurons from “chewing” motor neurons caused the mice to chew even in the absence of something to bite on. Thus, BDNF neurons attenuate chewing activity which is actually programmed to on by default.

This is why damage to the region of the brain where BDM neurons are located in humans can lead to eat too much.

“The evidence presented in our paper shows that the obesity associated with these lesions is the result of a loss of these BDNF neurons, and the results unify the known mutations that cause obesity into a relatively coherent circuit.” explain Jeffrey Friedman, molecular geneticist at Rockefeller University.

The simplicity of this circuit surprised the researchers because it is comparable to that of reflex behaviors like coughing, whereas eating was considered a much more complicated process. But this part of the brain is also involved in other automatic behaviors, such as fear and body heat regulation.

“What this paper shows is that the line between behavior and reflex is probably fuzzier than we thought,” concludes Friedmann.

This research was published in Nature.

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