Study reveals sequential neuronal activation regulating food intake

The process of food intake appears to be organized at the cellular level like a relay race: during eating, the baton is passed between different teams of neurons until we have consumed the appropriate amount of energy. This is the conclusion of a recent study by researchers at the Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU). Through this complex mechanism, the brain likely ensures that we neither eat too little nor too much. Malfunctions of this process may lead to eating disorders such as anorexia or binge eating. The findings appear in the Journal of Neuroscience.

To survive, we need to regularly replenish our energy by eating. This process is coordinated in the hypothalamus, an important control center in the brain. The hypothalamus constantly receives important information from our body and environment, such as whether it is day or night, or whether our blood sugar levels are low. Based on this data, it triggers certain innate behaviors, such as going to bed when it's dark or heading to the refrigerator when we're hungry.

But how does the brain make sure we don't stop eating once the initial hunger subsides and stretch receptors in the stomach signal that food has arrived? "When we eat, we quickly switch from what we call 'appetitive' behavior to 'consummatory' behavior," says Prof. Dr. Alexey Ponomarenko who holds the Professorship of Systemic Neurophysiology at the Institute of Physiology and Pathophysiology at FAU. "We know little about how the brain controls the duration of this consummatory phase. It should neither be too long nor too short so that we receive the right amount of energy."

Led by Prof. Ponomarenko, the FAU scientists together with a team from the University Hospital of Cologne investigated what happens in the brain during eating. The researchers studied the mouse hypothalamus, which is similar in structure to the human hypothalamus. "We analyzed the electrical activity of a specific region of the hypothalamus using an artificial intelligence method," explains mathematician Mahsa Altafi, a doctoral student at FAU and a joint senior author of the study. "This allowed us to determine which neurons fire – that is, generate electrical impulses – at specific times during food intake."

Sequential activation of four teams of neurons

The scientist was able to identify four distinct teams of neurons that become active in sequence during the eating process. These groups of neurons work together much like relay runners, each participating in different phases of the race. "We suspect that these teams weigh the information they receive from the body differently – for example, the blood sugar level, the amount of hunger hormones, and how full the stomach is," says Prof. Ponomarenko. The fourth team, for example, might give more weight to the stretch sensors than the first team. "That's how the hypothalamus may ensure we eat neither too little nor too much."

The researchers also looked at how the neurons within each team communicate with each other. It has long been known that neurons have a rhythm of activity: there are times when they are particularly excitable and times when they barely fire. These phases alternate regularly-often tens of times per second or more. To communicate, neurons must oscillate in the same rhythm. It's like using a walkie-talkie: both devices must be tuned to the same frequency or you'll only hear static.

"We were now able to show that the teams of neurons involved in food intake all communicate on the same frequencies," says Prof. Ponomarenko. "In contrast, groups of neurons responsible for other behaviors – such as exploring the environment or social interaction – prefer to communicate on a different channel." This probably makes it easier for the neurons involved in eating to exchange information and stop the eating process at the right time. This finding may even have therapeutic potential: it is already possible to influence the rhythm of neurons from the outside, for example through oscillating magnetic fields. Perhaps the communication of these "feeding teams" could be improved in this way. If successful, this could help alleviate eating disorders – at least that is the long-term hope.

In mice, the oscillatory behavior of neurons can be influenced even more directly by optogenetic manipulations. We are now planning a follow-up study to investigate how this affects their feeding behavior."

Prof. Dr. Alexey Ponomarenko, FAU scientist