The Amrein laboratory seeks to understand how peripheral sensory systems detect and process external stimuli and how such information is conveyed to the central nervous system in order to generate appropriate behavioral responses. Our work focuses mainly on the chemosensory system, especially taste, using Drosophila melanogaster as a model organism. The detection of chemical cues is crucially important for identifying suitable food sources, avoiding potential foods contaminated with harmful compounds, locating oviposition sites, and identifying of and discriminating between potential mating partners and mate competitors, respectively. Many of these behaviors demand also sensory input from other systems, including the olfactory, visual, auditory and somatosensory systems. Thus, a related interest of our laboratory is to identify network connections between the different sensory pathways that participate in these behaviors.
More recently, we have begun to investigate processes that affect behavioral and physiological processes in response to neuropeptide action. Neuropeptide signaling pathways, many of which are conserved between mammals and insects, affect virtually all types of behaviors by modulating the physiological states of organ systems (brain, muscle, gut, heart etc).
Why Drosophila
A typical insect brain has a few hundred thousand neurons and orders of magnitude more synapses. While the Drosophila CNS is simple and very small compared to that of humans (or even mice) fruit flies are capable of a multitude of extraordinary behavioral tasks that mimic many behaviors observed in vertebrate animals. And like mammalian behavior, insect behaviors can be modified through different experiences and show remarkable plasticity. The features that make Drosophila melanogaster the insect model system of choice are many: they include vast genetic resources and molecular-genetic manipulability, cost effective maintenance, molecular and physiological processes, many of which are conserved in vertebrates and availability of well-established behavioral assays.
The Drosophila gustatory system
The peripheral gustatory sensory system of insects, unlike that of mammals, is distributed throughout all major body parts. In Drosophila, the main taste organ are a pair of labial palps located at the tip of the proboscis (the ‘insect tongue’). Each palp is covered with a stereotypical array of 31 taste sensilla, containing between 2 to 4 gustatory receptor neurons (GRNs). A row of GRNs containing taste pegs lines the medial side of each palp, at the entrance of the feeding tube (pharynx). Along the pharynx, three internal taste clusters monitor and evaluate nutrients as they are ingested and pass into the esophagus and eventual the gut. In addition, the fly like many other insects has between thirty to fifty taste sensilla on each of the six legs and the anterior wing margin.
GRNs are primary sensory neurons. Their cell bodies are located at the base of each sensillum; each neuron extends a single dendrite, loaded with receptor proteins, into the bristle cavity. Taste chemicals enter the bristle through a pore at its tip and are then solubilized in the lymph in which the dendrite loaded with receptor proteins is bathed. At the proximal end of the GRNs, an axons extends towards the brain. Axons are bundled into the gustatory nerve and connect in the sub-esophageal zone (SEZ) with second order taste and interneurons. Second order projection neurons send axons to the superior lateral protocerebrum in the central brain, where taste information is further processed, decoded and conveyed to motor circuits for appropriate behavioral output.
Gustatory Receptors
Soluble chemicals are detected by gustatory receptor (GR) proteins. Similar to insect olfactory receptors (ORs), GR proteins contain 7 hydrophobic transmembrane segments. Indeed, the genes encoding ORs and GRs have a common ancestor, Olfactory receptor co-receptor (ORCO), and are also structurally related to one another. Thus, GRs –like ORs – are likely to have an inverse membrane topology when compared to classical G- protein coupled receptors (GPCRs), with an intracellular amino terminus and an extracellular carboxy terminus. GR signaling is similar to that of ORs, and GRs were shown to function primarily as ligand-gated ion channels. Based on expression, the Gr genes can be broadly divided into two classes: Grs expressed in appetitive neurons (i.e. activated by sugars), and Grs expressed in avoidance (i.e. activated by bitter compounds and high concentration of salt). We use molecular genetics, combined with behavioral and live neural imaging methods to reveal the function of individual Gr genes. These analyses established that a small, highly conserved subfamily of eight Gr genes encode receptors for sugars, while the majority of the remaining Gr genes encode receptors for aversive bitter compounds.
A few Gr genes, in addition to the sugar Gr genes, are highly conserved among insects, suggesting that these encode receptors that serve important functions shared by many different species. Indeed, one such group (the Gr28 subfamily) has been a research focus of our group over the last several years, leading to the discovery of a novel, and what appears to be an insect specific taste modality for RNA and ribonucleosides.
A second major group of taste receptors was identified and characterized by a number of investigators, including our group. These receptors belong to the Ionotropic Receptor (IR) family and were shown to be important for the detection of carboxylic acids and fatty acids, as well as the detection of volatile compounds in the olfactory system.
Neuropeptides
Neuropeptide signaling pathways, some of which are conserved between mammals and insects, are important to regulate many physiological processes, and in in turn, can affect behavioral outputs. The fly genome has more than 40 neuropeptide genes, many of which encode multiple neuropeptides generated from pro-peptides, and for most these peptides, receptors have been identified. Yet, for many neuropeptides and their receptors, detailed understanding of how they convey their activity to their target tissue and beyond has remained elusive. Most neuropeptide receptors belong to the G -protein coupled receptor family, and they can be expressed within or outside the CNS. Our recent work revealed that the gluconeogenic enzyme Glucose 6 phosphatase (G6P) has been appropriated for modulating the release of several NPs in the Drosophila neurosecretory system. A group of closely related neuropeptides, the FMRFamides, are of special interest, because we found that they are G6P dependent signaling molecules that regulate and co-ordinate glycogen metabolism in muscle tissues. Specifically, FMRFamides and their cognate receptor, FMRFaR, are necessary to build up glycogen stores in jump muscles, muscles that control all leg-based locomotion.
The Amrein Laboratory at Texas A&M University 