Columbia Team Identifies Brainstem Neurons that Command Mice to Stop Eating

Columbia University researchers have discovered specialized neurons in the mouse brainstem that directly instruct the animals to cease eating. These cells, distinct from other appetite-regulating circuits, integrate sensory and physiological cues to determine satiety. Located in the evolutionarily ancient brainstem, the neurons could inform future obesity therapies.

Alexander Nectow, co-senior author on the paper published in Cell, explains “These neurons are unlike any other neuron involved in regulating satiation. 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.”

Using spatially resolved molecular profiling, a method enabling precise cell identification, the team isolated the neurons in a brain region linked to complex signal processing. “This technique allows you to see cells where they are in the brainstem and what their molecular composition looks like,” Nectow notes.

When activated via light-controlled experiments, the neurons caused mice to eat smaller meals. “Interestingly, these neurons don’t just signal an immediate stop; they help the mice to slow down their eating gradually,” says Srikanta Chowdhury, co-lead researcher. The cells responded to appetite hormones and GLP-1 agonists, drugs used for obesity. Activation by GLP-1 analogs enhanced their tracking of each bite, while hunger hormones silenced them.

“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 adds. “And ultimately, they leverage all of this information to decide when enough is enough.”

Though identified in mice, the neurons’ brainstem location—shared across vertebrates—suggests humans likely possess similar cells. “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 says. “And we hope that it could be used for obesity therapies down the road.”