Scientists at Columbia University have found specialized neurons in the brains of mice that command the animals to stop eating. Although many feeding circuits in the brain are known to play a role in monitoring food intake, the neurons in these circuits do not make the final decision to stop eating. The neurons identified by the Columbia scientists, a new element of these circuits, are located in the brainstem, the oldest part of the vertebrate brain. Their discovery could lead to new treatments for obesity.
Unknown Cells in the Brain Involved in Appetite Regulation
“These neurons are unlike any other neurons involved in the regulation of satiety,” says Alexander Nectow, a physician-scientist at Columbia University’s Vagelos College of Physicians and Surgeons, who led the research with Srikanta Chowdhury, a research associate in the Nectow lab. “Other neurons in the brain are normally limited to recognizing what food we eat, how the food fills the gut or what nutrients are extracted from the food. The neurons we found are special in that they seem to integrate all this different information and more.”
The decision to stop eating is a well-known phenomenon. “It happens every time we sit down to eat: At a certain point during the meal we feel full, then we get even fuller and then we get to a point where we think, okay, that’s enough,” say the researchers. How does the brain know when the body has had enough – and how does it react to this information to stop eating? Other researchers had previously traced the decision cells back to the brain stem, but the traces ended there.
Nectow and Chowdhury used new single-cell techniques that make it possible to look into a region of the brain and recognize different cell types that were previously difficult to distinguish from each other. According to the researchers, this technique – spatially resolved molecular profiling – makes it possible to see cells where they are located in the brainstem and what their molecular composition looks like. By profiling a brainstem region known for processing complex signals, the researchers discovered previously unknown cells that had similar properties to other neurons involved in appetite regulation.
Therapies Against Obesity
To see how the neurons influence eating behavior, the researchers engineered the neurons so that they could be turned on and off by the researcher using light. When the neurons were activated by the light, the mice ate much smaller meals. The intensity of the activation determined how quickly the animals stopped eating. Interestingly, these neurons not only signaled an immediate stop, but also helped the mice to gradually slow down their eating. Nectow and Chowdhury also investigated how other food circuits and hormones influenced the neurons.
The researchers found that the neurons were silenced by a hormone that increases appetite and activated by a GLP-1 agonist, a class of drugs now popular for treating obesity and diabetes. These experiments revealed that these inputs helped the neurons track every bite of food the mice ate. Essentially, these neurons can smell food, see it, feel it in the mouth and gut, and interpret any gut hormones that are released in response to eating it. And ultimately, they use all this information to decide when enough is enough.
Although the specialized neurons were found in mice, Nectow says their location in the brainstem, a part of the brain that is essentially the same in all vertebrates, suggests that humans most likely have the same neurons. The researchers believe this is an important new starting point for understanding what it means to be full, how it comes about, and how it can be used to finish a meal. And they hope that it can be used for obesity therapies in the future.
Why We Reach for Food
Our motivation to eat is controlled by a complex network of cells in the brain that use signals from the body as well as sensory information about the food in front of us to determine our behavior. Scientists at Scripps Research have identified a group of neurons in a small and little-studied region of the brain – the parasubthalamic nucleus (PSTN) – that controls when an animal decides to take a first bite of food.
In a study published in Molecular Psychiatry , the team of scientists set out to selectively manipulate a group of PSTN cells that increase their activity during periods of binge eating. Other scientists have observed that many PSTN cells become active after a large meal, but the team wondered how these cells might influence appetite. The research team found that the set of cells that respond to binge eating can drastically change the behavior of mice.
Research Findings Could be Relevant for Eating Disorders
Hungry mice normally start eating quickly as soon as they have food available. But when the researchers activated this set of PSTN cells, the mice began eating much more slowly and, surprisingly, drinking water much more quickly. These results show that this specific group of PSTN cells controls the early stages of hunger-driven decision making before actual eating occurs. By manipulating even smaller groups of cells within the PSTN, the team was able to identify exactly which cell groups were responsible for delayed eating and accelerated drinking.
They also discovered that another group of PSTN cells triggered a different effect, urging the mice to eat more sweets. These research findings could be relevant to eating disorders in which people have either too much or too little control over the onset of food intake – the decision to give in to the first bite or wait longer. Aside from food and water, similar mechanisms could play a role in the loss of control over the use of reward substances such as drugs.