Neurons discovered that tell us when to stop eating

Researchers at Columbia University have discovered a unique group of neurons in the mouse brain that command the animal to stop eating. 

While many brain circuits monitor food intake, these neurons – located in the brainstem, one of the oldest regions of the vertebrate brain – appear to make the final decision to end a meal. This breakthrough finding may open new avenues for developing obesity treatments.

Neurons sense eating behavior 

Alexander Nectow is a physician-scientist at Columbia University Vagelos College of Physicians and Surgeons, who led the research with Srikanta Chowdhury, an associate research scientist in the Nectow lab.

“These neurons are unlike any other neuron involved in regulating satiation,” said Nectow. 

“Other neurons in the brain are usually restricted to sensing food put into our mouth, or how food fills the gut, or the nutrition obtained from food. The neurons we found are special in that they seem to integrate all these different pieces of information and more.”

The final step in meal termination

The process of ending a meal is something everyone experiences – at some point during eating, a signal builds, and we decide, “That’s enough.” 

While previous studies have pinpointed brain circuits that monitor various aspects of food intake, they did not identify the specific cells responsible for actually stopping the eating process. 

Previous leads had traced this decision-making capability to the brainstem, but the precise neurons remained unidentified until now.

Nectow and his team employed advanced single-cell techniques that enable researchers to distinguish between cell types in complex brain regions. This method, called spatially resolved molecular profiling, allowed them to observe cells in their native environment and determine their molecular makeup.

“This technique – spatially resolved molecular profiling – allows you to see cells where they are in the brainstem and what their molecular composition looks like,” Nectow explained.

During their detailed examination of a brainstem region known for processing complex signals, the team discovered a set of cells with characteristics resembling other appetite-regulating neurons. But what do these neurons actually do?

How neurons control eating behavior 

To investigate the role of these neurons in controlling food intake, the researchers used optogenetics – a method that allows cells to be activated or deactivated by light. 

When these newly discovered neurons were stimulated with light, the mice responded by eating significantly smaller meals. 

Moreover, the degree of light activation determined how quickly the mice reduced their food intake, suggesting that these neurons not only signal an immediate stop but also help modulate the pace at which eating slows down.

“Interestingly, these neurons don’t just signal an immediate stop; they help the mice to slow down their eating gradually,” Chowdhury said.

The experiments revealed that these cells track every bite the mice take by integrating sensory cues from the mouth, the gut, and even visual signals of food. Their coordinated activity underlies the decision-making process that eventually leads to satiety.

Interactions with other neural signals

The researchers also probed how these neurons interact with other known components of feeding regulation. They found that the neurons are silenced by a hormone that increases appetite, and conversely, they are activated by GLP-1 agonists – a class of drugs that is increasingly used for treating obesity and diabetes. 

These observations indicate that the neurons respond to a broad range of signals, effectively “sensing” food through multiple channels and integrating this information to decide when enough food has been consumed.

“Essentially these neurons can smell food, see food, feel food in the mouth and in the gut, and interpret all the gut hormones that are released in response to eating,” Nectow said. “And ultimately, they leverage all of this information to decide when enough is enough.”

Implications for obesity treatments

Although these specialized neurons were discovered in mice, their location in the brainstem – an area highly conserved among vertebrates – strongly suggests that humans possess similar cells. 

This finding represents a major new entry point for understanding satiety and could lead to innovative therapies for obesity by targeting the neural circuitry responsible for stopping food intake.

“We think it’s a major new entry point to understanding what it means to be full, how that comes about, and how that is leveraged to end a meal,” Nectow added. “And we hope that it could be used for obesity therapies down the road.”

By identifying and characterizing these neurons, Columbia scientists have taken a significant step toward unraveling the complex neural mechanisms underlying hunger and satiety. 

As further research is conducted to explore these pathways in humans, new treatments for obesity and related disorders may emerge, offering hope for those struggling with excessive food intake.

The study is published in the journal Cell.

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