Researchers discover specific taste neurons necessary for protein craving in fruit flies

A team of neuroscientists from the Champalimaud Centre for the Unknown (CCU), in Lisbon, Portugal, has discovered that were it not for specific taste neurons located in the fruit fly's proboscis (the equivalent of our tongue), the fly would not develop a craving for protein even when in excruciating need of it. The results, published in the journal eLife, could represent a step towards preventing the transmission of certain insect-borne human diseases.

The team had already shown that flies can develop a craving for proteins when they are deprived of essential amino-acids, that is, when they lack the protein building-blocks that their organism is unable to synthesize. But the neuronal mechanisms involved were not known.

In the new study, led by Carlos Ribeiro and whose first authors are Kathrin Steck and Samuel Walker, the scientists now show that this involves changes in the taste system - and identify two groups of neurons that are necessary for this protein craving.

The team set out to search for the sensory neurons that accounted for the appetite that flies develop for yeast when they are amino-acid deprived. Yeast is the main natural protein source for fruit flies, and flies eat protein when lacking essential amino-acids.

"The first step was to systematically silence different neurons in the fly to look for the ones which, when turned off, eliminated the protein-deprived fly's appetite for yeast", explains Ribeiro.

Indeed, the authors found that silencing specific taste neurons inhibited flies' appetite for yeast. This was true even when protein needs were at their highest: the females used in this part of the study were mated, and therefore had a large demand for protein for the production of eggs.

Actually, the scientists identified two different sets of taste neurons involved in the insects' yeast appetite: one on the outside of the proboscis and one on its inner surface.

They then confirmed the role of the identified taste neurons by recording their activity when they were fully functional. "We showed that in the amino-acid-deprived fly, if you put yeast on their tongue, you see a specific reaction to yeast in those taste neurons", says Ribeiro.

"We were surprised to see that the response of those taste neurons to yeast was increased after flies were fed on a diet lacking amino acids", notes Ribeiro. The team was not expecting that such a change in response to the same taste, depending on the fly's hunger, could happen at such an early stage in sensory processing, that is, right at the tip of the tongue. "The neurons became very sensitive to yeast and they fired very strongly" in the presence of yeast.

According to Ribeiro, this means that these specific proboscis neurons make yeast taste much better to the animals lacking amino-acids, thus accounting for their yeast craving. "These neurons change the way the fruit fly sees the world", he notes.

Besides amino-acid status, flies' craving for protein is influenced by another important internal state: their mating state. This is because after flies mate, they start producing eggs, and this egg production absolutely depends on ingestion of protein. "Pregnant female flies eat much more protein than virgin females because they need to make eggs", says Ribeiro.

Surprisingly, though, the team found no effect of the reproductive state of the fly on the taste neurons' activity, whether they were amino-acid satiated or deprived . "This is one of the first studies", says Ribeiro, "to show that mating changes the way the fly tastes the world at a different level of the brain", and not at the level of the tongue. A result, he adds, that "is very important for neuroscience", insomuch as many different internal states affect behavior but it is not known precisely how the signals from each of them are integrated by the brain to produce a particular behavior.

Eat and keep on eating

But there's more. The team further showed that each of the two sets of neurons regulated a different part of the insects' feeding behavior. This novel result, says Ribeiro, was possible only with the "flyPAD", a technology that had been developed by the laboratory at the CCU. "The flyPAD allows us to see very precisely how the animal eats", he explains. "It uses touch-screen technology like that in your iPad or iPhone".

More specifically, the scientists discovered that the taste neurons on the outside of the proboscis were responsible for the initiation of the feeding behavior, while the ones on the inside sustained the feeding behavior. "The first set makes the fly start to eat yeast, telling it it is the right food, and the second set tells it to keep on eating it, that yeast is still the right food", Ribeiro summarizes.

If similar taste neurons were also at play in the mosquito's protein craving, this could have implications in terms of controlling malaria and other mosquito-borne diseases. For the most part, mosquitoes live on nectar: only females sting animals and humans because they absolutely need protein from their blood to lay eggs.

"If mosquitoes have similar taste neurons as flies, a chemical which would block those taste neurons in female mosquitoes could cancel this craving", says Ribeiro, thus preventing the transmission of the malaria parasite from insect to person. "This would be an interesting contribution to stopping the spread of many deadly diseases."