Even in an unchanging world we might not experience the same sensations twice. The smell of freshly baked bread can make us ravenous when we're hungry, but nauseous when full; the sight of beer might make us thirsty at the end of a long day, but rather less so the morning after. This flexibility in behaviour enhances animals’ chances of survival by tuning their actions to what produces the most beneficial outcome at any given time. Drosophila melanogaster provides an interesting example of this phenomenon: starved flies are more sensitive to attractive odours, such as low levels of vinegar, allowing them to detect food sources more efficiently. At the same time, they are less sensitive to repulsive odours, such as CO2, allowing them to ignore potentially toxic compounds. How could this seemingly paradoxical response be implemented?
A team of researchers at the University of California, San Diego, has addressed this question in a study recently published in eLife. The authors had two prime candidate peptides for the opposing responses: sNPF and tachykinin, two molecules that are implicated in behavioural responses to nutrition. In the first experiment, they tested whether removing the receptor for these molecules in olfactory neurons affected the reaction of starved flies to attractive and repulsive odours.
They found that removing these receptors had almost opposite effects: without the sNPF receptor starved flies were attracted less to an attractive odour, but without the tachykinin receptor they were repulsed less by a repellent odour. This suggests that each of these signals is responsible for one of the opposite changes in behaviour that starvation induces; so how do these signals affect the processing of olfactory information? The simplest mechanism would be to have each peptide specifically affect the connections between those olfactory neurons that sense attractive or repulsive odours with their respective partner neurons. In order to find out whether this theory was correct the team removed the receptor for sNPF in olfactory neurons that sense the attractive odour and removed the tachykinin receptor from those that sense the repulsive odour.
The sensitivity changes followed the predictions from the simplest mechanism: attraction was attenuated in flies in which the sNPF receptor was removed from attractant-sensing neurons and repulsion was enhanced in flies in which the tachykinin receptor was removed from repellent-sensing neurons. These results suggest that sNPF specifically sensitizes attraction, whereas tachykinin specifically dampens aversion.
So, how does starvation recruit these peptides to modulate olfaction? In previous studies, Drosophila insulin was found to be a sensor of the nutritional state of the animal. When the team inhibited insulin signalling in the repellent olfactory neurons, they noticed that fully fed animals displayed starved-like behaviour – an effect that could be blocked by inhibition of the receptor for tachykinin. This suggests that, in starved animals, lower levels of insulin signalling directly potentiate the tachykinin receptor within a subset of olfactory neurons and thereby repress aversion.
This study shows how the nutritional state can affect the processing of sensory information and can lead to the fine-tuning of behaviour. The peptides described in this study have homologues in mammals, making a case as clear as ever that what is found in the fly, could be found in man.
