How the nervous system controls eating behavior

Brazilian professor at Yale University reveals mechanisms used by sensory cells in gastrointestinal tract to communicate with the brain and stimulate the desire to consume caloric food.

By Elton Alisson  |  Agência FAPESP – How does the nervous system control eating behavior so that some time after we eat a certain food, usually caloric, we are led to want to eat it again by taste, smell and other sensations?

This question intrigues Brazilian researcher Ivan de Araujo, associate professor of Psychiatry and of Cellular & Molecular Physiology at the Yale School of Medicine in the United States. After graduating from the University of Brasília (named after Brazil's capital city) he earned a master’s degree from the University of Edinburgh (UK) and a PhD from the University of Oxford (UK).

To find answers, Araujo has performed a number of studies with the aim of identifying neural circuits associated with hunger, satiety, palatability, and the pleasure provided by food, as well as investigating the mechanisms whereby the nervous system controls eating behavior.

At the end of September Araujo visited Brazil to participate as a speaker in the São Paulo School of Advanced Science on Reverse Engineering of Processed Foods, held at the University of Campinas’s Food Engineering School (FEA-UNICAMP).

One of the aims of the event, which was supported by FAPESP under its São Paulo School of Advanced Science (SPSAS) program, was to discuss novel ways of developing processed foods that can help solve health problems or increase satiety to reduce caloric intake, for example.

“What interests me, basically, is to better understand where the motivation to consume nutrients comes from and to try to find out what kind of information is transmitted by the nervous system when we ingest a food, remember it later, and want to consume it more and more,” Araujo told Agência FAPESP.

Araujo and his group initially studied the gustatory system to find out how sensations reach the brain from the oral cavity and modify our eating behavior. 

In exploratory experiments with mice genetically modified to be unable to taste nutrients such as sugar, they discovered that even so, the animals displayed preferences for certain foods as a function of their nutritional value instead of their palatability.

“This was the first sign that the nervous system must have some kind of code through which the brain can distinguish between a sensory stimulus arising in the oral cavity and a nutritional stimulus from the gastrointestinal tract,” Araujo said. 

In collaboration with colleagues at the University of São Paulo’s Biomedical Science Institute (ICB-USP) and the Federal University of the ABC’s Center for Mathematics, Computation & Cognition (CMCC-UFABC), he tested this hypothesis in a series of experiments with mice, showing that different neural circuits are involved in experiencing the pleasure of eating and in recognizing the caloric and nutritional value of food. 

Neural circuits in the ventral striatum are responsible for perceiving the pleasure or reward (hedonia) derived from food with a sweet taste, for example, whereas circuits in the dorsal striatum recognize the caloric and nutritional value of sweet food, according to the researchers who worked on the study (read more at agencia.fapesp.br/22800). The group included Tatiana Lima Ferreira, a scientist from CMC-UFABC awarded a scholarship abroad by FAPESP for a postdoctoral research internship in Araujo’s lab at Yale.

“We found a kind of division of labor in the brain’s dopaminergic reward system,” Araujo said, referring to neurons that trigger the release of dopamine, a neurotransmitter associated with pleasure and reward. “Certain cells appear interested in food palatability, while others respond more specifically to nutritional value, in terms of the quantity of calories or metabolites in the food in question. Taste and nutritional value are dissociated and encoded differently, and in parallel in the central nervous system, by this group of cells that compute the reward from ingestion.”

Connection with gastrointestinal tract

The experiments with mice also pointed to the possibility of some kind of connection between the gastrointestinal tract and the central nervous system’s reward mechanism. 

When nutrients were introduced into the animals’ gastrointestinal tract, their brains released dopamine. “We knew there was a biological connection between the presence of nutrients in the gastrointestinal tract and the increase in dopamine released by the brain, but we didn’t know which circuit connected these two factors,” Araujo said.

The answer was found in Aplysia, a genus of sea slugs widely used in experiments on food reward mechanisms because they are easily grown in the lab and have a relatively simple central nervous system, with only about 10,000 neurons, yet are capable of remembering and learning. Neurons that always do the same thing can be located in different exemplars of Aplysia, which is impossible in rodents, Araujo explained.

“Experiments with Aplysia have shown that the connections between neurons change when an animal learns something new,” he said. “Eric Kandel used Aplysia as a model in his research.” Kandel, an Austrian-born American neuroscientist, won the 2000 Nobel Prize in Physiology or Medicine for research on learning and memory.

In studies using Aplysia, Araujo and collaborators found that the neurons in the equivalent of the gastrointestinal tract’s vagus nerve released dopamine and that this modified the animal’s behavior.

Based on this finding, the researchers decided to investigate whether the same phenomenon occurred in mammals, which have a large vagus nerve that passes through much of the body from the brain to the abdomen and contains motor and sensory fibers.

“Although the vagus nerve in mammals doesn’t contain dopamine, we believed it somehow participated in the release of this neurotransmitter by the brain in mammals, too. This inspired us to look at this group of cells in the gastrointestinal tract,” Araujo said.

Through experiments in which they stimulate sensory cells of the gastrointestinal tract of mice with a laser beam, the researchers plan to identify the signaling pathway that connects the gastrointestinal tract with the brain’s reward system in mammals. 

“We want to describe this signaling pathway and to manipulate and acquire control over the sensory cells of the gastrointestinal tract, so that gastrointestinal sensations can be created experimentally using laser stimulation, for example,” Araujo said.

Preliminary results of the experiments indicate that laser stimulation of these cells activates the brain’s reward system, according to Araujo. “The classical understanding of the vagus nerve is that it acts to restrict consumption,” he said. “But actually, it tells the brain that an important event has occurred. The animal remembers this later and acts accordingly.”

The discovery could pave the way to the development of foods that efficiently stimulate this group of sensory cells in the gastrointestinal tract in order to reduce caloric intake.

Araujo said the discovery of sensory cells in the gastrointestinal tract and the receptors they express could be the basis for the development of foods that maximize their activity so that the brain does not initiate compensatory behavior to contribute to an increase in caloric intake.