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Unlike humans, most animals rely heavily on scents to collect information about their external environment, and in particular assess the friendly or not-so-friendly nature of encounters with other animals. For example, chemical signals (including pheromones) play an important role in the detection of a mating partner nearby, or of a competing male, and of predators looking for food. The robust and stereotyped behavioral responses triggered by pheromones in insects and vertebrates have fascinated scientists for more than a century. However, the molecular and neural basis of how these chemosignals are perceived in mammals haveremained unclear until recently.

In our study published in the journal Nature, the result of a collaborative work between the Dulac and the Murthy labs, we made significant progress towards understanding the functions of receptors expressed in a chemosensory organ called the vomeronasal organ (VNO). This olfactory structure exists in most terrestrial vertebrates (but not in higher primates or humans) and has been implicated in detecting chemical cues essential for social and defensive behaviors. In particular, previous work including data from the Dulac lab showed that the genetic inactivation of the VNO in mice causes defects in sex discrimination and aggressive behavior.

The mouse VNO expresses more than 250 receptors that detect social and defensive cues. The cloning of vomeronasal receptors originated in 1995 (Dulac and Axel 1995), but the function of only three receptors had been characterized so far. In our study, we used high-throughput imaging to systematically identify the function of different receptor. We succeeded in matching more than 80 receptors with their cognate, biologically relevant cues, for example male or female scents, predators or competing sympatric species.

The specialization of receptor function identified in our study is remarkable. For example, we found receptors that specifically detect mammalian predators and another set of receptors that only detect snakes. Importantly, we found that each receptor is specifically tuned to a signal for a physiological process (such as glucocorticoids for stress and estrogens for estrous and pregnancy) or sex/species identity (male, female or predator) of the emitter. The mouse is therefore using a remarkably targeted approach to extract biologically relevant information from the environment.

Our study immediately raises a new wave of questions. For example, how does the animal brain use specific vomeronasal cues to generate behaviors? The newly identified collection of receptors implicated in behaviorally relevant contexts will greatly facilitate future study, and experiments to address how receptor inputs are integrated into brain circuits are currently underway.

Read more in Nature

Read more in HARVARDgazette

[October 5th, 2011]

View Catherine Dulac’s Faculty Profile

View Venkatesh Murthy’s Faculty Profile

(l to r) Yoh Isogai, Catherine Dulac, Venkatesh N. Murthy, and Vikrant Kapoor

(l to r) Yoh Isogai, Catherine Dulac, Venkatesh N. Murthy, and Vikrant Kapoor