Carrion smell is strongly repugnant to humans and triggers distinct innate behaviors in many other species. This smell is mainly carried by two small aliphatic diamines, putrescine and cadaverine, which are generated by bacterial decarboxylation of the basic amino acids ornithine and lysine. Depending on the species, these diamines may also serve as feeding attractants, oviposition attractants, or social cues. Behavioral responses to diamines have not been investigated in zebrafish, a powerful model system for studying vertebrate olfaction. Furthermore, olfactory receptors that detect cadaverine and putrescine have not been identified in any species so far. Here, we show robust olfactory-mediated avoidance behavior of zebrafish to cadaverine and related diamines, and concomitant activation of sparse olfactory sensory neurons by these diamines. The large majority of neurons activated by low concentrations of cadaverine expresses a particular olfactory receptor, trace amineassociated receptor 13c (TAAR13c). Structure-activity analysis indicates TAAR13c to be a general diamine sensor, with pronounced selectivity for odd chains of medium length. This receptor can also be activated by decaying fish extracts, a physiologically relevant source of diamines. The identification of a sensitive zebrafish olfactory receptor for these diamines provides a molecular basis for studying neural circuits connecting sensation, perception, and innate behavior.Danio rerio | aversion | heterologous expression | polyamines C adaverine, putrescine, and other biogenic diamines are strongly repulsive odors to humans, for whom these odors presumably signal bacterial contamination. It may be expected that animal species feeding on carcasses attribute a more positive valence to diamines, and indeed both putrescine and cadaverine have been reported to be feeding attractants for rats (1) as well as goldfish (2). Similarly, insects depositing their eggs in carcasses or other proteineacous materials are attracted by these diamines (3). Beyond signaling danger or food, putrescine and cadaverine also serve as social cues in several vertebrate species, both for marking of territories-for example, in feline species (4)-and for burial of conspecifics (5).Very little is known about the molecular and cellular basis of cadaverine-driven behaviors. Cadaverine and putrescine evoke electrophysiological responses in the olfactory epithelium of two fish species (2, 6) and cadaverine-responsive olfactory sensory neurons and glomeruli have been identified in the mouse (7,8). However, chemosensory receptors that detect cadaverine or related diamines are unknown in any species, and could provide valuable tools to study how the olfactory system mediates innate aversion or attraction.Here, we show that cadaverine is a major product of zebrafish tissue decay, activates a zebrafish olfactory receptor (trace amineassociated receptor 13c, TAAR13c) with high affinity, and elicits a strong, low-threshold, and olfactory-mediated avoidance response in zebrafish. In vivo me...

The ability to find and consume nutrient-rich diets for successful reproduction and survival is fundamental to animal life. Among the nutrients important for all animals are polyamines, a class of pungent smelling compounds required in numerous cellular and organismic processes. Polyamine deficiency or excess has detrimental effects on health, cognitive function, reproduction, and lifespan. Here, we show that a diet high in polyamine is beneficial and increases reproductive success of flies, and we unravel the sensory mechanisms that attract Drosophila to polyamine-rich food and egg-laying substrates. Using a combination of behavioral genetics and in vivo calcium imaging, we demonstrate that Drosophila uses multisensory detection to find and evaluate polyamines present in overripe and fermenting fruit, their favored feeding and egg-laying substrate. In the olfactory system, two coexpressed ionotropic receptors (IRs), IR76b and IR41a, mediate the long-range attraction to the odor. In the gustatory system, multimodal taste sensation by IR76b receptor and GR66a bitter receptor neurons is used to evaluate quality and valence of the polyamine providing a mechanism for the fly’s high attraction to polyamine-rich and sweet decaying fruit. Given their universal and highly conserved biological roles, we propose that the ability to evaluate food for polyamine content may impact health and reproductive success also of other animals including humans.

Trace amine-associated receptors (TAARs) in mammals recently have been shown to function as olfactory receptors. We have delineated the taar gene family in jawless, cartilaginous, and bony fish (zero, 2, and >100 genes, respectively). We conclude that taar genes are evolutionary much younger than the related OR and ORA/V1R olfactory receptor families, which are present already in lamprey, a jawless vertebrate. The 2 cartilaginous fish genes appear to be ancestral for 2 taar classes, each with mammalian and bony fish (teleost) representatives. Unexpectedly, a whole new clade, class III, of taar genes originated even later, within the teleost lineage. Taar genes from all 3 classes are expressed in subsets of zebrafish olfactory receptor neurons, supporting their function as olfactory receptors. The highly conserved TAAR1 (shark, mammalian, and teleost orthologs) is not expressed in the olfactory epithelium and may constitute the sole remnant of a primordial, nonolfactory function of this family. Class III comprises three-fourths of all teleost taar genes and is characterized by the complete loss of the aminergic ligand-binding motif, stringently conserved in the other 2 classes. Two independent intron gains in class III taar genes represent extraordinary evolutionary dynamics, considering the virtual absence of intron gains during vertebrate evolution. The dN/dS analysis suggests both minimal global negative selection and an unparalleled degree of local positive selection as another hallmark of class III genes. The accelerated evolution of class III teleost taar genes conceivably might mark the birth of another olfactory receptor gene family.Danio rerio ͉ evolution ͉ in situ hybridization ͉ shark ͉ trace amine

A female’s reproductive state influences her perception of odors and tastes along with her changed behavioral state and physiological needs. The mechanism that modulates chemosensory processing, however, remains largely elusive. Using Drosophila, we have identified a behavioral, neuronal, and genetic mechanism that adapts the senses of smell and taste, the major modalities for food quality perception, to the physiological needs of a gravid female. Pungent smelling polyamines, such as putrescine and spermidine, are essential for cell proliferation, reproduction, and embryonic development in all animals. A polyamine-rich diet increases reproductive success in many species, including flies. Using a combination of behavioral analysis and in vivo physiology, we show that polyamine attraction is modulated in gravid females through a G-protein coupled receptor, the sex peptide receptor (SPR), and its neuropeptide ligands, MIPs (myoinhibitory peptides), which act directly in the polyamine-detecting olfactory and taste neurons. This modulation is triggered by an increase of SPR expression in chemosensory neurons, which is sufficient to convert virgin to mated female olfactory choice behavior. Together, our data show that neuropeptide-mediated modulation of peripheral chemosensory neurons increases a gravid female’s preference for important nutrients, thereby ensuring optimal conditions for her growing progeny.

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