HHMI scientists have discovered a command center in the brain that controls how much insects eat and how quickly they consume their food.
- HHMI researchers identify a set of neurons that monitors how hungry a fly is and how quickly it is eating.
- Rapid feedback from these cells helps ensure that the insects consume appropriate amounts of nourishing foods.
Working in fruit flies, Howard Hughes Medical Institute scientists have discovered a command center in the brain that controls how much insects eat and how quickly they consume their food. To make the decision, neurons in the command center integrate information about an animal's internal state of satiety with taste cues detected just moments after food is swallowed.
“There is this very small set of neurons whose job it is to simultaneously monitor how hungry the fly is and what the fly is ingesting,” says Leslie Vosshall, an HHMI investigator at The Rockefeller University who led the study. “They know if the fly is hungry or not hungry, and they also know if the fly is eating something really rich or something that's not very rich.” Rapid feedback from the cells helps ensure that the insects consume appropriate amounts of nourishing foods. Vosshall says a similar system might also regulate ingestion in vertebrates. Vosshall and her colleagues published their research March 31, 2016, in the journal Cell.
The study began seven years ago, when Nilay Yapici, a postdoctoral researcher in Vosshall's lab at Rockefeller, set out to find neurons or other factors that signal to a fly that it is hungry and should eat. To do that, she needed to compare exactly how flies eat under different circumstances, so she created an automated system to measure exactly how much fluid a fly sips from a slender glass tube. The system, called Expresso because it builds on a manual ingestion-monitoring method called CAFE, needed to track ingestion in real time, and it needed to differentiate between very small volumes of food.
It took five years of development to get Expresso working the way the team needed it to. But that work was essential for their subsequent experiments. “This assay allowed us to look at the tiny meals that these tiny animals eat and to see how flies interact with food,” Vosshall says.
Using Expresso to track flies’ consumption of sugar water, the scientists learned that hungry flies eat voraciously as soon as food becomes available, but slow down their feeding after a minute or so. “We could tell that somehow these animals know when they've eaten enough,” Vosshall says. Even if they hadn't eaten for a full day, however, the flies were choosy. Hungry flies enthusiastically gulped super-sweet water, but ate far less if they were offered a weaker sugar solution, snacking only occasionally. “Even when they're really hungry, they precisely control how much they eat,” Vosshall says. “They don't want to fill up on something that's not very sweet.”
Yapici found that this eating behavior changed, however, when a small group of neurons in the brain was inactive. When those cells were prevented from signaling, flies remained uninterested in food, even if they hadn't eaten in 24 hours. The researchers named the cells ingestion neurons (IN1), and devised a series of experiments to investigate how they worked.
Vosshall and Yapici found that IN1 cells receive input from taste neurons that are sensitive to sweet sensations—but these were not the taste-sensitive cells in the tongue. Instead, IN1 neurons connect to taste-sensitive cells in the pharynx, where food passes after it is swallowed. “As the food is being swallowed by the fly, these neurons are directly reporting information to the neurons that Nilay discovered,” Vosshall says. At the same time, she says, IN1 cells appear to communicate with central brain circuits that monitor an animal's energy needs.
Working with Raphael Cohn, a graduate student in Rockefeller neuroscientist Vanessa Ruta's lab, Yapici next used a microscope to peer inside flies’ brains as they ate, watching for pulses of activity within the IN1 neurons. The cells did not respond when the insects sipped plain water, nor did they react when a fly touched its tongue to a sweet solution. Well-fed flies could even sip a bit of sugar without triggering much of a response from the IN1 cells. But when a hungry fly ingested a sugary solution—even a tiny amount—the IN1 cells immediately became very active.
That activity quieted down as the flies ingested more sugar, but if the insects were not allowed to consume more than their first taste, the IN1 cells continued signaling insistently. In fact, Vosshall says, the cells remained active for seven minutes, during which time the flies kept sticking out their tongues, seeking more sugar. “We think that the activity of the IN1 cells is really tuning the drive to ingest,” Vosshall says. “The brain is telling these cells that the animal is still hungry, and the pharynx is telling the cells that the animal needs more. Then the activity of the cells ramps down as the flies approach satiation.”
Further supporting the idea that IN1 cells control an insect’s motivation to eat, the researchers showed that they could provoke a well-fed fly to eat as if it were hungry by artificially activating the cells. “This command center is really calling the shots to help these animals figure out if they've eaten enough,” Vosshall says.
Vosshall's research on how animals sense and respond to their environment has shifted to mosquitos since her team's work on IN1 cells began. It's been a gradual transition as her team develops research tools they need to investigate mosquito biology efficiently and begin to explore how the disease-carrying insects find humans and what drives their biting behavior. She says the new Cell publication reports on her lab's final work in flies, but she notes that the work raises questions she hopes other labs will explore.
There's reason to suspect that other animals might have similar mechanisms for monitoring and regulating ingestion, for instance. It's now known that taste cells in the stomach and intestines influence metabolism and appetite in humans and mice, and there's evidence that mice have taste-sensitive cells in their pharynxes, too. “We hope that this will open people's mind to the possibility that there are taste cells that lie between the tongue and the belly that could be playing this role,” she says. “What more perfect thing than to have this control mechanism as you're swallowing stuff, as a further check of what you're eating?”