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1. Chemical Communication in Mammals

In mammals, chemical communication plays an important role in various social interactions. Therefore, it would be an ideal experimental model to analyze the neural mechanisms underlying their natural behaviors and their "mind." We are currently studying the male effect pheromone, which stimulates the GnRH neurons of female goats; the alarm pheromone, which activates the anxiety circuit in the brain of other rats; and the appeasing pheromone, which suppresses the activation of the amygdala of other rats in response to threats. We believe that we can understand animals' natural lives more accurately when we analyze their chemical communication.

We have identified the pheromone in goats!:
We have identified 4-ethyloctanal as the pheromoe molecules responsible for male effect in goats. [Abstract]
The study has been featured in articles: [UTokyo Research], [Counsel & Heal], [Discover], [Discovery News], [EurekAlert!], [International Science Times], [LiveScience], [National Geographic], [Nature], [Phys.org], [Science]

Currently, we are conducting the following analyses.

Analyzing the production system:
As we have proved previously, pheromones are produced in an androgen-dependent manner. Therefore, we are applying the subtraction method to identify the genes which show idiocratic expression in the pheromone producing areas. We are also establishing a cultivating system for sebaceous gland cells, which eventually will lead us to producing pheromones in vitro.

Analyzing the perceiving system:
We carry out an extensive range of research, from cloning pheromone receptors to analyzing endocrine responses.


It is anecdotally known that other rats will not be captured in a trap that fails to kill an initial trapped rat. We hypothesize that the trapped rat alarms the other rats by means of olfactory signals. Studies have shown that such alarm odors or "alarm pheromones" appear to be an evolutionarily conserved signal because they are released by a variety of other mammalian species including mice, rats, deer, cattle, swine, and humans. By analyzing the “alarm pheromone” in rats, we found that stressed rats release the “alarm pheromone” from their perianal region and increase anxiety of recipient rats and induce a variety of anxiety-related responses depending on the experimental model.

We have identified the pheromone in rats!:
We have identified that a mixture of 4-methylpentanal and hexanal are the molecules responsible for increasing anxiety and serve as an anxiogenic pheromone in rats. [Open Access]
The study has been featured in articles: [UTokyo Research], [Chemical & Engineering News]

Currently, we are conducting the following analyses.

Identification of the receptors:
Because 4-methylpentanal is detected by the vomeronasal system, we are trying to identify the receptor for 4-methylpentanal, focusing on V1Rs expressed in the vomeronasal epithelium.

Analyses on the neural mechanisms of pheromone effects:
We found that 4-methylpentanal detection by the vomeronasal system requires simultaneous hexanal detection, most likely from the main olfactory system, to activate the bed nucleus of the stria terminalis. Therefore, information from the two olfactory systems should converge at a particular site between the olfactory bulb and the bed nucleus of the stria terminals. We are trying to elucidate this convergence.


In many species, the presence of a conspecific(s) mitigates stress responses. Although studies have focused on this phenomenon between mothers and pups (maternal buffering), and spouses (mate buffering), the presence of an adult same-sex conspecific also ameliorates stress responses in rats, sheep, cattle, monkeys, and humans; a phenomenon called "social buffering." We assume that organisms acquire the ability to induce and receive social buffering during their evolution, which subsequently promotes social behavior and may lead to gregariousness. We have analyzed the social buffering of stress responses using rats and found that non-stressed rats release volatile olfactory signals that induce social buffering in the stressed rat through the main olfactory system.

Currently, we are conducting the following analyses.

Identification of the responsible molecule(s) for social buffering:
We are attempting to identify the responsible molecule(s) by collecting the odor from non-stressed rats and analyzing it. We are also trying to find the source of the responsible odor. Such analyses would also reveal if the responsible molecule(s) meets the definition of pheromones.

Analyzing the neural mechanism of social buffering:
Using behavioral neuroscientific and electrophysiological methods, we are trying to understand how the olfactory signal suppresses the amygdala response to stressors.

Analyzing the factors required for social buffering:
We are trying to answer several "big questions" about social buffering, including why we see social buffering in some species, and what is the difference between animals that induce social buffering in rats and those that do not.


Copyright (C) Laboratory of Veterinary Ethology, The University of Tokyo.