A neuromodulatory mechanism for state-dependent nutrient detection in Drosophila

Feeding is an essential routine of an animal to survive. The decision of what to eat is a collective outcome of a sensory evaluation and its nutritional needs. While an animal may decide to eat food just because of its good taste, it is also possible that nutritional needs dictate what to eat through appetite or cravings. Pregnant females often report cravings that potentially arise from a dramatic change in their nutritional needs and physiological and hormonal state. Food sources attract the attention of many animals primarily by their smell (long range cue) and taste (short range cue). Those sensory cues help these animals to identify a food source and they use them to assess the nutritional value of the food. Due to changing internal needs, animals often make different choices elicited by the same chemosensory cue bouquet. However, little is known how exactly internal needs of an animal modulate its perception and its sensory systems. In this cumulative thesis, I present two published studies addressing this question by using an important class of nutrients, the polyamines. In the first study, I, in collaboration with colleagues, investigated polyamines as chemosensory cues and found that they are detected by both olfactory and gustatory systems of Drosophila as signals for beneficial food or egg laying sites. This multimodal polyamine detection is mediated by an ionotropic receptor, IR76b, along with a co-receptor (IR41a) in the olfactory system and by IR76b alone, or with a yet to be identified co-receptor, in the gustatory system. Moreover, female flies significantly increase their reproductive success if they are fed with polyamine enriched food. This finding has provided an entry point to the second paper, in which the role of the mating state in the perception of polyamines has been investigated. Surprisingly, mated female flies exhibit an enhanced attraction towards biologically relevant concentrations of polyamines. This finding is particularly interesting because the modulation takes place right at the sensory neuron level. Drosophila is an excellent model to dissect the molecular underpinnings of such a modulation, because of the available genetic toolboxes. By using genetic, behavioral and calcium imaging experiments it was possible to show that a G-protein coupled receptor, sex peptide receptor (SPR), and its ligands, the myoinhibitory peptides (MIPs) regulate this mechanism. Both SPR and MIPs are expressed in the polyamine sensitive OSNs and GSNs, and SPR expression significantly increases upon mating in sensory neurons thereby modulating their presynaptic output. Interestingly, SPR acts on OSNs’ and GSNs’ physiology in opposite directions. While increased SPR expression inhibits the presynaptic output of OSNs, GSNs undergo presynaptic facilitation. Altogether, both modulations serve the same behavioral output, to adjust the nutritional preference of the gravid female: enhanced polyamine preference. From the broader perspective, this study contributes to our understanding of the detection of essential nutrients and neuromodulation of sensory systems according to changing internal states and needs of an animal, including humans