“Food-seeking neurons” attributed as cause for post-meal cravings

20 Mar 2024 --- UCLA psychologists have pinpointed “overactive food-seeking neurons” as the potential cause behind post-meal snack cravings rather than an overactive appetite. While the study was performed in mice, the researchers suggest its implications may offer response tactics for human eating disorders.

The study, published in the journal Nature Communications, discovered a circuit in mice brains that makes them crave food and seek it out, even when they are not hungry. When stimulated, this cluster of cells propels mice to “forage vigorously” and prefer fatty and pleasurable foods like chocolate over healthier foods like carrots.

People also possess these cells, indicating these findings may offer “new ways of understanding eating disorders” if the same causality is confirmed in humans.

The report is the first to find cells dedicated to food-seeking in a part of the mouse brainstem typically associated with panic but not with feeding.

Brain cells dedicated to food-seeking
The report is the first to find cells “dedicated to food-seeking” in a part of the mouse brainstem typically associated with panic but not with feeding.

“This region we’re studying is called the periaqueductal gray, and it is in the brainstem, which is very old in evolutionary history and because of that, it is functionally similar between humans and mice,” says corresponding author Avishek Adhikari, a UCLA associate professor of psychology.

“Although our findings were a surprise, it makes sense that food-seeking would be rooted in such an ancient part of the brain, since foraging is something all animals need to do.”

Adhikari’s field of research involves studying how fear and anxiety help animals assess risks and minimize exposure to threats. His group made the discovery while trying to learn how this particular spot was involved in fear.

“Activation of the entire periaqueductal gray region causes a dramatic panic response in both mice and humans. But when we selectively stimulated only this specific cluster of periaqueductal gray neurons called vgat periaqueductal gray cells, they did not alter fear, and instead caused foraging and feeding,” adds Adhikari.

Working with fiber optics
The researchers injected a virus into mouse brains that was genetically engineered to make the brain cells produce a light-sensitive protein. When a laser shines on the cells via a fiber-optic implant, the new protein translates that light to electrical neural activity in the cells. 

A miniature microscope, developed at UCLA and affixed to the mouse’s head, recorded the neural activity of cells.

When stimulated with laser light, the vgat periaqueductal gray cells fired and “kicked the mouse into hot pursuit” of live crickets and non-prey food, even if it had just eaten a large meal. 

The stimulation also compelled the mouse to chase after moving objects that were not food, like ping pong balls, although it did not try to eat these objects. It also prompted the mouse to confidently explore everything in its enclosure.

“The results suggest the following behavior is related more to wanting than to hunger,” Adhikari says. “Hunger is aversive, meaning that mice usually avoid feeling hungry if they can. But they seek out activation of these cells, suggesting that the circuit is not causing hunger.”

If found in humans, the food-seeking circuit could become the treatment target for some kinds of eating disorders.“Instead, we think this circuit causes the craving of highly rewarding, high-caloric food. These cells can cause the mouse to eat more high-calorie foods even in the absence of hunger.”

Cells found in both mice and humans
Satiated mice with activated vgat periaqueductal gray cells craved fatty foods so much, they were willing to endure foot shocks to get them, something full mice normally would not do. 

Conversely, when the researchers injected a virus engineered to produce a protein that dampens the cells’ activity under exposure to light, the mice foraged less, even if they were very hungry.

“Mice show compulsive eating in the presence of aversive direct consequences when this circuit is active, and don’t search for food even if they’re hungry when it’s not active. This circuit can circumvent the normal hunger pressures of how, what and when to eat,” says Fernando Reis, a UCLA postdoctoral researcher who conducted most of the experiments in the research.

It was Reis who came up with the idea to study compulsive eating.

“We’re doing new experiments based on these findings and learning that these cells induce eating of fatty and sugary foods, but not of vegetables in mice, suggesting this circuit may increase eating of junk food,” he says.

Like mice, humans also possess vgat periaqueductal gray cells in the brainstem, the researchers highlight. They posit that if this circuit is overactive in a person, they might feel more rewarded by eating or crave food when not hungry. 

However, if this circuit is not active enough, they could have less pleasure associated with eating, potentially contributing to anorexia. “If found in humans, the food-seeking circuit could become the treatment target for some kinds of eating disorders,” the study concludes.

In other dietary research, an Australian study found very low-calorie diets are “safe” for severely obese adolescents under guidance despite recorded side-effects.

By Benjamin Ferrer