Reactions to stress vary between individuals, and physiological and behavioral responses tend to be associated in distinct suites of correlated traits, often termed stress coping styles. A connection between physiology, behavior, and cognition was recently demonstrated in strains of rainbow trout (Oncorhynchus mykiss) selected for consistently high or low cortisol responses to stress. Compared to high-responsive (HR) fish the low-responsive (LR) strain display better retention of a conditioned response, and tend to show proactive behavior such as enhanced aggression, social dominance, and rapid resumption of feed intake in new environments. Marked differences between HR and LR trout in brain monoamine neurochemistry have also been reported. In line with these studies, experiments with the lizard Anolis carolinensis reveal connections between monoaminergic activity in limbic structures, proactive behavior in novel environments, and the establishment of social status via agonistic behavior.Together these observations suggest that within-species diversity of behavioral and cognitive correlates of stress responsiveness is maintained by natural selection over a wide range of animal groups. This diversity may underlie several seemingly different phenomena such as stress coping style, behavioral syndromes, and animal personalities.

Predator-prey relationships provide a classic paradigm for the study of innate animal behavior. Odors from carnivores elicit stereotyped fear and avoidance responses in rodents, although sensory mechanisms involved are largely unknown. Here, we identified a chemical produced by predators that activates a mouse olfactory receptor and produces an innate behavioral response. We purified this predator cue from bobcat urine and identified it to be a biogenic amine, 2-phenylethylamine. Quantitative HPLC analysis across 38 mammalian species indicates enriched 2-phenylethylamine production by numerous carnivores, with some producing >3,000-fold more than herbivores examined. Calcium imaging of neuronal responses in mouse olfactory tissue slices identified dispersed carnivore odor-selective sensory neurons that also responded to 2-phenylethylamine. Two prey species, rat and mouse, avoid a 2-phenylethylamine odor source, and loss-of-function studies involving enzymatic depletion of 2-phenylethylamine from a carnivore odor indicate it to be required for full avoidance behavior. Thus, rodent olfactory sensory neurons and chemosensory receptors have the capacity for recognizing interspecies odors. One such cue, carnivore-derived 2-phenylethylamine, is a key component of a predator odor blend that triggers hard-wired aversion circuits in the rodent brain. These data show how a single, volatile chemical detected in the environment can drive an elaborate danger-associated behavioral response in mammals.kairomone | olfaction | pheromone | trace amine-associated receptors | G protein-coupled receptor P redator-prey relationships provide a classic paradigm for understanding the molecular basis of complex behavior (1). Predator-derived visual, auditory, and olfactory cues induce hardwired defensive responses in prey that are sculpted by strong evolutionary pressure and are critical for survival. For example, odors from felines, canines, and other predators elicit innate reactions in rodents, including stereotyped avoidance behaviors and stimulation of the hypothalamic-pituitary-adrenal axis that coordinates sympathetic stress responses (1). Aversive reactions to odors can function in reverse as well, as skunk thiols facilitate prey escape by repelling predator species (2).Predator odors contain a class of ecological chemosignals termed kairomones, cues transmitted between species that benefit the detecting organism. Predator odor-derived kairomones that elicit defensive responses in rodents are largely unknown and can be found in fur, dander, saliva, urine, or feces of divergent predator species. One volatile chemical produced by foxes, 2,5-dihydro-2,4,5-trimethylthiazole (TMT), and two nonvolatile lipocalins produced by cats and rats elicit fear-like or aversive behavior in mice, enabling remote or contact-based detection of predator cues (3-5). Each of these chemicals is not broadly produced by predators, raising the possibility that rodents detect a multitude of species-specific predator signals, each of which triggers a hardwir...

SUMMARY Background Rodents use olfactory cues for species-specific behaviors. For example, mice emit odors to attract mates of the same species but not competitors of closely related species. This implies rapid evolution of olfactory signaling, although odors and chemosensory receptors involved are unknown. Results Here, we identify a mouse chemosignal, trimethylamine, and its olfactory receptor, trace amine-associated receptor 5 (TAAR5), to be involved in species-specific social communication. Abundant (>1,000-fold increased) and sex-dependent trimethylamine production arose de novo along the Mus lineage after divergence from Mus caroli. The two-step trimethylamine biosynthesis pathway involves synergy between commensal microflora and a sex-dependent liver enzyme, flavin-containing monooxygenase 3 (FMO3), which oxidizes trimethylamine. One key evolutionary alteration in this pathway is the recent acquisition in Mus of male-specific Fmo3 gene repression. Coincident with its evolving biosynthesis, trimethylamine evokes species-specific behaviors, attracting mice but repelling rats. Attraction to trimethylamine is abolished in TAAR5 knockout mice, and furthermore, attraction to mouse scent is impaired by enzymatic depletion of trimethylamine or TAAR5 knockout. Conclusions TAAR5 is an evolutionarily conserved olfactory receptor required for a species-specific behavior. Synchronized changes in odor biosynthesis pathways and odor-evoked behaviors could ensure species-appropriate social interactions.

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