Researchers identify brain cells that delay the first bite of food

  • Food
  • July 11, 2024

Do you pick up a fork and take the first bite of pie, or do you say no and walk away? Our motivation to eat is controlled by a complex web of cells in the brain that use signals from inside the body, as well as sensory information about the food in front of us, to determine our behavior. Now, scientists at Scripps Research have identified a group of neurons in a small, understudied area of ​​the brain—the parasubthalamic nucleus (PSTN)—that controls when an animal decides to take the first bite of food.

In the study, published in Molecular psychiatry On July 4, 2024, 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.

“In our study, we used a technique that allowed us to activate cells in the brains of mice that were activated by a specific experience — in this case, binge eating,” says Jeff Dunning, PhD, a research associate at Scripps Research and first author of the new paper. “Once we have this ensemble of PSTN cells captured, we can flip them on like a light switch and watch what happens when the animals eat and drink.”

The research team found that the ensemble of cells sensitive to binge eating could dramatically alter the behavior of mice. Hungry mice normally quickly start eating food as soon as it becomes available to them. But when researchers turned on this ensemble of PSTN cells, mice were much slower to start eating and, surprisingly, much faster to start drinking water.

“Our results tell us that this particular group of PSTN cells guides the early stages of hunger-driven decision-making, before eating actually occurs,” Dunning said. “The effect on water drinking is somewhat counterintuitive, but it could be related to prandial thirst — the phenomenon where thirst is stimulated as soon as we start eating.”

By manipulating even smaller sets of cells within the PSTN, the team was able to pinpoint exactly which groups of cells were responsible for the delayed eating and the accelerated drinking. They also discovered that yet another group of PSTN cells produced a different effect, urging the mice to eat more sweet dishes.

“Overall, these results reveal that PSTN neurons exert a complex combination of functions,” said lead author Candice Contet, PhD, associate professor in the Department of Molecular Medicine at Scripps Research. “Several studies had previously shown that PSTN activity can limit the amount of food eaten, but the fact that certain PSTN neurons control the initiation of eating or drinking, or even promote “The consumption of 'treats' is completely new.”

Contet, Dunning and colleagues think their findings could be relevant to eating disorders, in which people have too much or too little control over the initiation of eating — the decision to indulge in that first bite or wait longer. In addition to food and water, similar mechanisms could be at play in the loss of control over the consumption of rewarding substances such as drugs, which the team is currently investigating.

In addition to Contet and Dunning, Catherine Lopez, Colton Krull, Max Kreifeldt, Maggie Angelo, and Leeann Shu of Scripps Research, and Charu Ramakrishnan and Karl Deisseroth of Stanford University are also authors of the study, “The parasubthalamic nucleus refeeding ensemble delays feed initiation and hastens water drinking.”

This work was supported by funding from the National Institutes of Health (AA026685, AA027636, AA006420, AA027372, and AA007456).

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