Research
The lab is broadly focused on using the fruit fly, Drosophila melanogaster, to understand fundamental principles of sensory processing and behaviour. Projects in the lab can be roughly divided into three main areas:
Peripheral taste
We have been particularly interested in the detection and coding of ionic tastes in the fly. In 2018, we published a systematic dissection of peripheral salt taste coding (Jaeger et al., 2018), where we used a combination of calcium imaging, neuroanatomy, and quantitative behaviour to demonstrate the roles of different taste neuron classes in salt taste. We showed that salt acts through a complex combination of taste pathways, making its coding fundamentally different from other primary taste modalities. We followed up by recently publishing the first unequivocal full molecular composition of a high salt taste receptor (McDowell et al., 2022). Here, we identified a set of three ionotropic receptors that together mediate cation non-specific aversive responses to high salt concentrations. We have also recently identified novel principles of peripheral acid taste (Stanley et al., 2021). We showed that lactic acid is particularly attractive to flies and acts through two distinct receptor families expressed in “sweet” neurons. Interestingly, these two receptor types mediate distinct temporal components of the lactic acid responses, with one driving activation by stimulus onset and another during stimulus removal. We are continuing to pursue the mechanisms and functions of peripheral taste detection.
Taste circuits
Early on, we identified two neuromodulatory mechanisms by which taste sensory neuron output is modulated. In the first case, we showed that bitter taste suppresses feeding in part by presynaptically inhibiting the output of sweet taste neurons, providing a mechanism of taste integration in mixtures (Chu et al., 2014). We also demonstrated that hunger desensitizes bitter taste by suppressing a facilitatory signal acting on bitter taste neuron output (LeDue et al., 2016). More recently, we developed a closed-loop optogenetic system for identifying and characterizing higher-order taste circuit neurons (Musso et al., 2019). We have used this system to dissect the contributions of different classes of higher-order neurons to taste behaviour, screened for additional circuit components (Lau et al., 2021), and developed a novel optogenetic taste memory paradigm for understanding the impact of experience on taste sensitivity and behaviour (Jelen et al., 2021). Our current focus is on investigating the tuning and functions of second-order taste neurons in the fly brain.
Nutrient sensing
We were among several groups to uncover early evidence that ingested nutritional sugars evoke taste-independent positive effects on fly feeding (Stafford et al., 2012). We continued this work by identifying an important role for pharyngeal taste inputs – located in the first part of the digestive tract – in monitoring the nutritional quality of foods during ingestion and either sustaining or terminating feeding (LeDue et al., 2015). Most recently, we have identified a three-part neural circuit that integrates information about two key dietary sugars: glucose and fructose (Musso et al., 2021). We showed that glucose circulating in the hemolymph acts as a tightly-regulated satiety signal that controls activity in a set of central glucose-sensing neurons of the fly brain. Those glucose-sensing neurons release a neuropeptide that modulates the sensitivity of central fructose-sensing neurons in the brain. When a fly feeds on sugar, fructose levels rise rapidly and stimulate these central fructose sensors to promote further feeding, but only when the fly is hungry. This neural link between two sugar sensors promotes tight control over nutrient intake to match energy needs. We continue to be interested in how the fly brain uses information about incoming nutrients.