Mammalian pheromone sensing

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The traditional distinction that the mammalian main olfactory system recognizes general odor molecules and the accessory (vomeronasal) system detects pheromones is no longer valid. The emerging picture is that both systems have considerable overlap in terms of the chemosignals they detect and the effects that they mediate. Recent investigations have discovered large families of pheromonal signals together with a rich variety of specific receptor systems and nasal detection pathways. Selective genetic targeting of these subsystems should help to unravel their biological role in pheromone-mediated behavioral responses.

Introduction

Pheromones are potent molecular signals that are fundamental for species-specific chemical communication, thus organizing a wide range of social behaviors such as finding and identifying a mate, regulating the level of aggression and social dominance, and mediating the recognition of kin and non-kin. Recent results have revolutionized our understanding of the organization of pheromonal communication in mammals, especially in the mouse, where a combination of gene targeting methodology with sophisticated physiological and behavioral analyses has led to a series of rapid advances.

Broader aspects of pheromonal communication in vertebrates have been summarized in several excellent articles [1, 2, 3, 4, 5, 6, 7, 8, 47, 48, 49, 70]. In this review, we will focus on the mechanisms underlying pheromone sensing in the periphery of the mouse olfactory system. The results reveal that the mouse nose employs a wide range of receptor- and signal transduction mechanisms for the sensing of vital chemosignals. The extent of the cellular and molecular heterogeneity in pheromonal detection pathways is unexpected, but this finding is mirrored by recent progress showing that the repertoire of chemical signals used for mammalian communication is equally heterogeneous (Box 1). Hence, the extent of receptor gene families and cellular detection mechanisms involved in mammalian pheromone sensing might reflect a need for the processing of large and very complex families of social recognition signals. The data summarized here indicate that we are just at the beginning of painting a comprehensive picture of this fascinating diversity.

Section snippets

Vomeronasal organ

It has been known since the 1970s that the mammalian vomeronasal organ (VNO) plays a pivotal role in the detection of chemical stimuli of social nature including pheromones [1]. However, defining the molecular nature of these cues proved surprisingly difficult. The advent of large-scale neurophysiological recording and imaging techniques in the mouse VNO [9, 10, 11] and accessory olfactory bulb (AOB) [12], together with genetic targeting of specific neurons and their signal transduction

Conclusions

A few years ago, a colleague gave the advice to leave the peripheral olfactory system behind and look for new challenges, mainly because ‘there was not much left to discover’. The evidence summarized above shows that nothing could be further from the truth. Of particular importance during the upcoming years will be to generate a more complete understanding of the role that each of the nasal subsystems play in chemosignal-evoked behavioral changes. It should be possible to define many of the

Update

Two recent studies shed new light on the chemosensory role of GC-D neurons by recording from genetically-labeled GC-D cells. Leinders-Zufall et al. [71] demonstrate that GC-D neurons recognize the peptide hormones uroguanylin and guanylin as well as natural urine stimuli. Furthermore, they show that these stimuli are transduced by an excitatory, cGMP-mediated signaling cascade that requires both GC-D and the cGMP-gated channel subunit CNGA3 [71]. In a parallel study, Luo and colleagues [72]

References and recommended reading

Papers of particular interest, published within the annual period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgement

Work in the authors’ laboratories is supported by the Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 530. T.L.-Z. is the awardee of a Lichtenberg-Professorship of the VolkswagenStiftung.

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