By hijacking connections between neurons deep within the brain, scientists forced full mice to keep eating and hungry mice to shun food. By identifying precise groups of cells that cause eating and others that curb it, the results begin to clarify the intricate web of checks and balances in the brain that control feeding.
“This is a really important missing piece of the puzzle,” says neuroscientist Seth Blackshaw of Johns Hopkins University in Baltimore. “These are cell types that weren’t even predicted to exist.” A deeper understanding of how the brain orchestrates eating behavior could lead to better treatments for disorders such as anorexia and obesity, he says.
Scientists led by Joshua Jennings and Garret Stuber of the University of North Carolina at Chapel Hill genetically tweaked mice so that a small group of neurons would respond to light. When a laser shone into the brain, these cells would either fire or, in a different experiment, stay quiet. These neurons reside in a brain locale called the bed nucleus of the stria terminalis, or BNST. Some of the message-sending arms of these neurons reach into the lateral hypothalamus, a brain region known to play a big role in feeding.
When a laser activated these BNST neurons, the mice became ravenous, voraciously eating their food, the researchers report in the Sept. 27 Science. “As soon as you turn it on, they start eating and they don’t stop until you turn it off,” Stuber says. The opposite behavior happened when a laser silenced BNST neurons’ messages to the lateral hypothalamus: The mice would not eat, even when hungry.
The results illuminate a complex network of neuron connections, in which some cells boost other neurons’ activity, while other cells apply brakes. In the experiment, stimulating BNST neurons with light — which consequently shut down the activity of neurons in the lateral hypothalamus — led to the overeating behavior, the team found. That result suggests that these lateral hypothalamus neurons normally restrict feeding.
That finding is surprising, says Blackshaw. Earlier experiments hinted that these hypothalamic cells would encourage eating behavior, but the new study suggests the exact opposite.
The researchers don’t know whether, if they controlled the neurons for long periods, the mice would ultimately starve or overeat to the point of illness. Stuber and colleagues used the laser technique, called optogenetics, in roughly 20-minute bursts. Longer-term manipulations of these neural connections — perhaps using a drug — might cause lasting changes in appetite and, as a result, body mass, Stuber says.
This precise control of feeding behavior underscores the fact that eating disorders occur when brain systems go awry, Stuber says. “We think of feeding in terms of metabolism and body stuff,” he says. “But at the end of the day, it’s controlled by the brain.”
When a laser activated a particular group of neurons, mice immediately began to eat. When the light turned off, the animals quit eating. Credit: Josh Jennings