The neuronal and molecular basis of quinine-dependent bitter taste signaling in Drosophila larvae

Abstract

The sensation of bitter substances can alert an animal that a specific type of food is harmful and should not be consumed. However, not all bitter compounds are equally toxic and some may even be beneficial in certain contexts. Thus, taste systems in general may have a broader range of functions than just in alerting the animal. In this study we investigate bitter sensing and processing in Drosophila larvae using quinine, a substance perceived by humans as bitter. We show that behavioral choice, feeding, survival, and associative olfactory learning are all directly affected by quinine. On the cellular level, we show that 12 gustatory sensory receptor neurons that express both GR66a and GR33a are required for quinine-dependent choice and feeding behavior. Interestingly, these neurons are not necessary for quinine-dependent survival or associative learning. On the molecular receptor gene level, the GR33a receptor, but not GR66a, is required for quinine-dependent choice behavior. A screen for gustatory sensory receptor neurons that trigger quinine-dependent choice behavior revealed that a single GR97a receptor gene expressing neuron located in the peripheral terminal sense organ is partially necessary and sufficient. For the first time, we show that the elementary chemosensory system of the Drosophila larva can serve as a simple model to understand the neuronal basis of taste information processing on the single cell level with respect to different behavioral outputs.

Bitter tastant responses in the amoeba Dictyostelium correlate with rat and human taste assays

“…The ability to recognize and/or respond to bitter tastants is shared amongst phylogenetically diverse groups, including mammals (Stern et al, 2011), amphibians (Go, 2006;Mashiyama et al, 2014), fishes (Ishimaru et al, 2005), cephalopods (Darmaillacq et al, 2004), decapod crustacea (Aggio et al, 2012), insects and nematodes (Hilliard et al, 2004;Gordesky-Gold et al, 2008;Apostolopoulou et al, 2014). However, data presented here suggest a conserved response from the unicellular Dictyostelium to primates; the last common ancestor of Dictyostelium and multicellular animals existed about a billion years ago (van Egmond and Van Haastert, 2010).…”

Pharmacological analysis of the feeding response of codling moth (Cydia pomonella; Lepidoptera: Tortricidae) neonates to bitter compounds

“…This fi nding corresponds well with earlier postulates that ligand-gated ion channels are needed for bitter-taste perception in insects (Yarmolinsky et al, 2009;Apostolopoulou et al, 2014;Liman et al, 2014;Choi et al, 2016).…”

“…As mentioned in the Introduction, it is not clear whether insect bitter-taste receptors signal through G-protein-dependent second messenger cascades or operate as ligand-gated ion channels (Yarmolinsky et al, 2009;Apostolopoulou et al, 2014;Liman et al, 2014;Choi et al, 2016). Noteworthy, the putative bitter-taste receptors of Drosophila fl ies share no sequence relationship with G-protein receptors.…”

“…Although, originally, these receptors were anticipated to function as G-protein coupled receptors, it is still not clear whether they signal through G-protein-dependent second messenger cascades or operate as ligand-gated ion channels (Yarmolinsky et al, 2009;Apostolopoulou et al, 2014;Liman et al, 2014;Choi et al, 2016). Less is known about bitter-taste perception by lepidopterous larvae.…”

Application of isothermal titration calorimeter for screening bitterness-suppressing molecules of quinine

“…Quinine is one of highly bitter drugs and it is widely used as bitter compounds for sensory experiments of both human and animals (Apostolopoulou, Mazija, Wust, & Thum, 2014;Keast, 2003;Ley, Krammer, Reinders, Gatfield, & Bertram, 2005;Roitman, Wheeler, & Carelli, 2005). According to our pilot experiments of human sensory experiments using several common bitter substances (quinine, caffeine and acetaminophen), high bitterness intensity can enhance discrimination between original solution and mix solution (data not shown).…”