Using an optogenetics approach, researchers at the Howard Hughes Medical Institute have uncovered sets of neurons that activate or inhibit eating behavior in mice. The findings may have implications for eating disorder treatments in humans.
A team headed by Scott Sternson, a group leader at the Janelia Farm Research Campus, used optogenetic tools to activate neuron sets that caused mice to either eat voraciously or not eat at all.
Sternson and his group targeted neurons that had previously been suspected of influencing eating motivation, both positively and negatively. They did this via optogenetics: they first injected mice with a transgene and a viral vector that specifically enabled these relevant neurons to be excited by light impulses. Then, using an optical fiber implanted into the target area of the brain, blue pulses of light were used to activate the neuronal circuits of interest.
“As soon as the fiber was in place, we saw that [our target] worked,” said Sternson, “because as we flashed the light on the brain of a sleeping mouse, it woke up and started eating with a voracious intensity, like it had been starving.”
Rather than acting as an ignition switch on self-propagated eating behavior, these appetite-controlling neurons appear to moderate eating behavior from moment to moment, according to the team. “What really surprised me, and what I find most interesting, is that these neurons act more like a gas pedal,” said Sternson, “where the level of neuron activation gave a proportional response.”
Since their optogenetics technique provided the researchers with precise temporal and spatial control of the circuits, they were able to stop stimulation of eating-activation neurons during feeding. In response, the animals usually stopped eating as well, which supports Sternson’s gas pedal theory.
The specificity of optogenetics was essential to the study, said Sternson, adding that in principle, the technique could aid the development of future treatments of eating disorders in humans. While the methods of the study may be too invasive for human application (an optical fiber would need to be implanted deep in the brain where eating regulatory neurons are located), the team’s findings have contributed to a better understanding of eating motivation in mammals.
“Whether that leads to refinement of molecular targeting for drug-like therapeutics or a better understanding of the psychological underpinnings of this kind of behavior, it will have an influence treatment of patients who have under- or overeating disorders,” says Sternson.