A Rodent-Repelling Odor: Feral Olfactory Communication Mechanisms Exposed Cory Camasta

Pheromones Pheromones are airborne hormones released by an organism that allow inter- and intra- species communication via olfactory pathways in the brain. Pheromones are utilized by single-celled prokaryotes, plants, and all the way up the evolutionary ladder to humans. Some bees and other insects have been known to communicate over distances of many miles using these chemicals. In rodents and other animals attuned to their olfactory senses, the pheromone profile of desecrations can instinctively convey to the smeller the gender, threat level, and relative time that the desecrating animal passed by (among other things). This is probably why dogs seem to enjoy smelling poop so much.

Olfactory Signal Transduction in Rodents (At a Glance) nose G-Protein mediated action potential cascade transduces the signals to the vomeronasal organ (VNO) via ion flux. The VNO in primates is not as developed as those in olfactory-attuned animals, so we effectively skip the preprocessing and go straight to the next step. Applicable molecules enter the nose and find their way to specific odorant receptors, sometimes with the help of Odorant Binding Proteins (OBPs). Some signals converge, but all make it to glomeruli in the olfactory bulb. Combinations of glomeruli send their signals to the olfactory epithelium, where the data is consolidated. The signal(s) then travels from the olfactory bulb to the amygdala and/or the hypothalamus where the brain interprets it and acts accordingly.

2-phenethylamine (PEA): The carnivore’s mark Gas phase @ B3LYP/MidiX

Alarm Pheromone: 2-phenylethylamine 2-phenethylamine has been shown to act as a Kairomone in rodents (interspecies signal). The compound is found in the urine of many predacious species. It is found in the urine of many other animals as well (since it is a metabolite of phenylalanine), but is often 50-500 or more times more concentrated in carnivores. The study in (1) finds that lion urine that has been stripped of this compound does not elicit the alarm response in rodents, while the whole urine does, as well as an extract of 2-phenethylamine. This would mean that, while it is probably not the only compound at work, 2-phenethylamine is definitely playing a large role in the alarm response.

The Neurojargon 2-phenethylamine has been found to interact with Trace Amine-Associated Receptors (TAARs, most notably TAAR4), among other targets. The study in (1) found that the major pheromone action of this compound can probably be attributed to its activity in the dorsal (and a little bit in the ventral) olfactory epithelium in the rodents’ brains. This tissue is associated with the innate behavioral response to aversive odors, and also expresses TAAR4 receptors. 2-phenethylamine was shown to target multiple sites in this region. Most humans find the odor displeasing, but it has not been shown to evoke an alarm response.

Neurojargon Continued This graphic shows the active areas of the olfactory center in mice exposed to food (left) and to fox urine (right). Olfactory glomeruli are the major signal transduction centers between the nose and the brain. The study in (3) found, by mutating certain areas of the olfactory center with a diphtheria gene in mice, that the dorsal region is primarily where innate, aversive olfactory responses are handled. By “knocking out” glomeruli in this region, mice appear to lose their innate fear of predators. They can still form new glomerular structures, however, following conditioning. These structures most likely allow for the storage of “scent memory” in mammals by association with other signaling pathways. ← Kobayakawa et al.

Molecular Mimicry: 2,4,5-trimethylthiazoline (TMT) and 2-sec-butyl-4,5-dihydrothiazole (SBT) Gas phase @ B3LYP/MidiX TMT – a component of fox urine and powerful kairomone SBT – an innate rodent pheromone that signals danger

The Biojargon When we examine the structures of the aformentioned pheromones and kairomones, in particular, we can see various evolutionary mechanisms at work. First we note that TMT and PEA are metabolic by-products found in the excretions of some carnivorous species. We then note the similarities of TMT, a kairomone, with SBT, an intraspecies pheromone, and the versatility of PEA as a precursor to a whole host of other neurotransmitters. Looking back on our knowledge of biology and chemistry, we begin to see a pattern emerge that probably has something to do with natural selection…

Biojargon Continued The similarities of the compounds to one another and other metabolic intermediates allow for relatively quick evolutionary adaptation. Consider that a mutation may cause a substituted residue or a whole new gene fragment, which will cause a small (usually insignificant) change in the structure of proteins. We know that the shape of a protein is one of the most important factors in determining what binds to it, so this does turn out to be significant over time. Prey that can sense their predators from far away have an obvious advantage over those that cannot, thus the better innate “smellers” will be more likely to survive and pass on their genes.

Works Cited 1. Ferrero, David et al. Detection and avoidance of a carnivore odor by prey. Proc Natl Acad Sci U S A. 2011 July 5; 108(27): 11235–11240. Published online 2011 June 20. doi:  10.1073/pnas.1103317108. 2. Brechbühl, Julien et al. Mouse alarm pheromone shares structural similarity with predator scents. Proc Natl Acad Sci U S A. 2013 March 19; 110(12): 4762–4767. Published online 2013 March 4. doi:  10.1073/pnas.1214249110. 3. Kobayakawa et al. Innate versus learned odour processing in the mouse olfactory bulb. Nature, Volume 450, p503-508 (2007). 4. He, Jie et al. Distinct Signals Conveyed by Pheromone Concentrations to the Mouse Vomeronasal Organ. J Neurosci. 2010 June 2; 30(22): 7473–7483. 5. Liman, Emily. Use it or lose it: molecular evolution of sensory signaling in primates. Pflügers Arch - Eur J Physiol. 2006 June 14. 6. Shah, Nirav. Fragrance Chemistry. 3rd Year Seminar. 2001 February 22.