Newly identified brain circuit could be target for treating obesity
Nerve cells that control overeating are distinct from those active in normal feeding, study shows
WELL CONNECTED Neurons (green) in the lateral hypothalamus connect with those in the ventral tegmental area of mice’s brains to contribute to compulsive sugar consumption.
Courtesy of Edward Nieh/MIT
Manipulating specific sets of brain cells can quash a mouse’s overindulgence of sugar.
The cells are part of a previously unknown brain circuit that controls compulsive sugar consumption in mice, researchers report in the Jan. 29 Cell. This circuit appears to be distinct from the one that controls normal eating, suggesting that it could be a target for treating obesity caused by overeating in humans.
“One of the biggest challenges with treating obesity that comes with compulsive overeating disorder is that most treatments are just a Band-Aid, treating the symptoms instead of the core problems,” says MIT neuroscientist Kay Tye. “The real underlying problems are the cravings that lead to compulsive eating and the behavior of compulsive overeating itself.”
Compulsive overeating is similar to drug addiction. Both are reward-seeking behaviors. Past work has linked drug addiction and other reward-seeking behaviors, such as sex and eating, to nerve cells, or neurons, connecting the lateral hypothalamus to the ventral tegmental area in the brain. Whether the neurons that control compulsive overeating also control normal eating has not been clear. The new study suggests that different brain circuits control the eating behaviors.
“This is exciting because one big difference between food addiction and drug addiction is that you don’t need drugs to survive. You do need food to survive,” Tye says. “The treatment of food addiction has to be more delicate, because you want to shut down the compulsive overeating, but you need to keep the desire to eat healthy food to survive intact. Our study suggests this is possible.”
Neurons send messages using molecules and electrical signals, linking different brain regions in a way similar to an electrical circuit. Tye and her colleagues used optogenetics, a technique for controlling brain cells with light, to determine that the compulsive consumption circuit was separate from the normal feeding circuit.
In one experiment, the team placed a sugary treat at the opposite end of a floor designed to deliver mild shocks to the mice’s feet. When neurons in the newly identified circuit were activated with light, the mice would brave the shocks and go for the treat. “They seemed to think it was worth it,” Tye says. When the neurons were deactivated, or shut off, the mice skipped the shocks and the sugar.
In a second experiment, the team put fully fed mice in an open chamber with easy access to food. When their compulsive eating neurons were activated, the mice hung around the chow longer. Then, when the scientists kept the mice away from food to make them hungry and shut the neurons off, compulsive sugar seeking dropped off but normal eating didn’t change. The result suggests that the compulsive eating circuit is distinct from the normal eating one.
A second paper in the Jan. 29 Cell supports the results. In this study, researchers from North Carolina and California recorded neuron activity in the lateral hypothalamus. One set of cells was active when a mouse poked its nose into a slot to search for a high-calorie treat. A separate set was active when the mouse took a lick of the high-calorie treat.
“Differentiating the two sets of neurons opens the door for us to start looking at the precise cellular architecture in these brain regions and how it controls behavior,” says study coauthor Garret Stuber, a neurobiologist at the University of North Carolina at Chapel Hill.
Gina Leinninger, a neurophysiologist at Michigan State University in East Lansing, says that both teams have presented elegant data. “The data suggest that, rather than looking at neurons in the lateral hypothalamus area as all doing the same thing, we need to realize that there are different types of neurons in the region that exert different control over behavior,” she says.
Tye says the next logical step is to determine the precise activation patterns of neurons in the overeating circuit during cravings and compulsive behaviors. Scientists could use this information to manipulate the neurons in the circuit and stop compulsive behavior before it starts, which could lead to new treatments for overeating and obesity.
GOING FOR IT At first, a mouse has no reservations about seeking a sweet treat from a port (upper right) in the wall. When the gridded floor is programmed to deliver mild shocks to the mouse’s feet, however, the animal won’t go for the treat. Then, scientists activate the mouse’s compulsive eating circuit with light through the wire attached to its head. In response, the mouse braves the shocks and goes for the treat.
Courtesy of Edward Nieh/MIT
