Have you ever started rooting around in your pantry immediately after a delicious dinner? Don’t blame your appetite. New research suggests you may have overactive food-seeking neurons in your brain.

Psychologists from UCLA have found a circuit in the brains of mice that makes them want and look for food, even if they’re not hungry. When activated, this cluster of cells urges mice to hunt for fatty, highly palatable foods like chocolate instead of healthy foods like veggies.

People have similar cells in their brains, which could help scientists understand eating disorders better. This research was published in Nature Communications. It’s the first to find cells associated with food-seeking in a part of the mouse brainstem usually linked with panic, but feeding.

"This region we're studying is called the periaqueductal gray (PAG), 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," said 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 an ancient part of the brain since foraging is something all animals need to do."

Adhikaria’s research is involved in learning about fear and anxiety. He and his colleagues discovered food-seeking behavior when evaluating risks to reduce exposure to threats.

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

The brains of mice were injected with a genetically engineered virus to make their brains produce a light-sensitive protein. Using a fiber-optic implant, a laser shines on the cells and a new protein transforms the light to electrical brain activity. The neural activity in the mice’s brains was recorded using a tiny microscope attached to the mice’s heads.

Once the brain cells were stimulated by the laser light, the mice went foraging for live crickets and non-pray food, despite recently consuming a large meal. The stimulation also led the mice to follow moving objects that were not food such as ping pong balls. However, they didn’t try to eat them, they just explored their surroundings more.

"The results suggest the following behavior is related more to wanting than to hunger," Adhikari said. "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. 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."

Mice who were full and possessed activated ygat PAG cells wanted high-fat foods so much, that they would accept food shocks to obtain them, something mice would not normally do. On the flip side, when the scientists used an engineered virus to make a protein that reduces the cell’s activity under light exposure, the mice sought out food less, even if they were overly 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," said Fernando Reis, a UCLA postdoctoral researcher who did most of the experiments in the paper and 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."

Similar to mice, humans also have vgat PAG cells in the brainstem. When this circuit is overactive, a person may feel rewarded by eating or desiring food when not hungry. If this circuit isn’t active enough, a person may have less pleasure in eating, which could contribute to anorexia nervosa. If found in people, this circuit could be used to treat eating disorders.

If you or your clients are eating compulsively or not eating at all, help is available. Below is a list of resources:

Overeaters Anonymous: Home - Overeaters Anonymous (oa.org)

National Eating Disorders Association: Get Help - National Eating Disorders Association

Better Help: BetterHelp - Get Started & Sign-Up Today

Equip Virtual Eating Disorder Treatment: Virtual Eating Disorder Treatment (equip.health)

Help Guide: Binge Eating Disorder - HelpGuide.org

Share Well Now: ShareWell | Mental Health Support | Peer Support (sharewellnow.com)

National Association of Anorexia and Associated Disorders: The National Association of Anorexia Nervosa and Associated Disorders - ANAD (eatingdisorderhope.com)

National Institute of Mental Health: Eating Disorders - National Institute of Mental Health (NIMH) (nih.gov)

Lisa Andrews, MEd, RD, LD

Reference:

1. Fernando M. C. V. Reis, Sandra Maesta-Pereira, Matthias Ollivier, Peter J. Schuette, Ekayana Sethi, Blake A. Miranda, Emily Iniguez, Meghmik Chakerian, Eric Vaughn, Megha Sehgal, Darren C. T. Nguyen, Faith T. H. Yuan, Anita Torossian, Juliane M. Ikebara, Alexandre H. Kihara, Alcino J. Silva, Jonathan C. Kao, Baljit S. Khakh, Avishek Adhikari. Control of feeding by a bottom-up midbrain-subthalamic pathway. Nature Communications, 2024; 15 (1) DOI: 10.1038/s41467-024-46430-5